Medicina

ARTICOLI RECENTI PUBBLICATI IN PUBMED SUL TEMA "FERTILITY PRESERVATION"

(aggiornamento del 6 marzo 2013)

 

1. J Gynecol Obstet Biol Reprod (Paris). 2013 Feb 28. pii: S0368-2315(13)00033-1.
doi: 10.1016/j.jgyn.2013.01.003. [Epub ahead of print]

[Fertility preservation among patients with cancer: Report of a French regional
practical experience.]

[Article in French]

Préaubert L, Poggi P, Pibarot M, Delotte J, Thibault E, Saias-Magnan J, Courbière
B.

Pôle de gynécologie-obstétrique et reproduction (Pr-Gamerre), hôpital de La
Conception, AP-HM, 147, boulevard Baille, 13385 Marseille, France. Electronic
address: lisepreaubert@free.fr.

OBJECTIVE: Improvement in cancer treatments has led to reconsider the importance
of quality of life after cancer, especially concerning maintening the potential
of fertility since it is often altered after healing. Our objective was to
estimate the knowledge and practices of the physicians in the field of Oncology
in a French Region (Provence Alpes- Côte d'Azur). PATIENTS AND METHOD:
Prospective survey, conducted between January and April 2012, amongst oncologists
working in Provence Alpes Côte d'Azur region, through questionnaires distributed
during multidisciplinary meetings in oncology. RESULTS: Among 225 replies, 54% of
the physicians had sent no patient to any oncofertility consultation during the
previous six months (n=120). Besides, 33% of the oncologists (n=68) declared they
had difficulties in addressing their patients to oncofertility consultation, and
58% of them (n=39) considered they lacked information on techniques and
indications of fertility preservation. CONCLUSION: This study provides an
estimation of the current practices in PACA region concerning oncofertility and
underlines the physicians' need of information. In this context, the regional
oncology network has set up a regional network « cancer and fertility » in order
to facilitate the access to fertility preservation prior to any potentially
sterilizing treatment for all patients.

Copyright © 2013. Published by Elsevier Masson SAS.

PMID: 23453919  [PubMed – as supplied by publisher]

2. Eur J Cancer. 2013 Feb 26. pii: S0959-8049(13)00106-8. doi:
10.1016/j.ejca.2013.01.032. [Epub ahead of print]

Ovarian tissue cryopreserved for fertility preservation from patients with Ewing
or other sarcomas appear to have no tumour cell contamination.

Greve T, Wielenga VT, Grauslund M, Sørensen N, Christiansen DB, Rosendahl M,
Yding Andersen C.

Laboratory of Reproductive Biology, Rigshospitalet – Copenhagen University
Hospital, Denmark. Electronic address: tinegreve@gmail.com.

AIM: The chemotherapy required to treat patients with sarcoma may as a
side-effect induce infertility in girls and young women. If these patients have
ovarian cortical tissue cryopreserved prior to chemotherapy, they may, if
necessary, have the tissue transplanted and restore their fertility. The aim of
this study was to evaluate the risk of residual cancer cells in the ovarian
cortex intended for transplantation. PATIENTS AND METHODS: Ovarian tissue stored
for fertility preservation from 16 surviving patients diagnosed with sarcoma
(nine with Ewing sarcomas, four with osteosarcomas, two with synovial sarcomas
and one with chondrosarcoma) was evaluated for the presence of malignant cells by
histology and by transplantation to immunodeficient mice for 20weeks. A fraction
of the tissue from patients with Ewing sarcoma was also evaluated for the
presence of the molecular marker EWS-FLI1 by reverse transcription quantitative
polymerase chain reaction (RT-qPCR). The transplant itself and selected murine
organs were analysed for the presence of malignant cells by histology. RESULTS:
All the mice accommodated the human tissue for 20weeks of transplantation period
with none of the mice developing any sign of cancer. In no instance were any
cancer cells detected by histology or RT-qPCR. CONCLUSION: Ovarian tissue from
patients with sarcoma appears to be without metastatic malignant cells in numbers
that allow detection. Although the actual pieces of ovarian tissue used for
transplantation remain unchecked, the current data indicate that the procedure is
safe at least in patients that survive the sarcoma disease.

Copyright © 2013 Elsevier Ltd. All rights reserved.

PMID: 23452988  [PubMed – as supplied by publisher]

3. Curr Oncol. 2013 Feb;20(1):e1-3. doi: 10.3747/co.20.1193.

Effect of cancer on ovarian function in patients undergoing in vitro
fertilization for fertility preservation: a reappraisal.

Levin I, Almog B.

Department of Gynecology and Sarah Racine ivf Unit, Lis Maternity Hospital,
Sourasky Medical Center, Affiliated to the Sackler School of Medicine, Tel Aviv
University, Tel Aviv, Israel.

PMCID: PMC3557336
PMID: 23443918  [PubMed – in process]

4. Am J Obstet Gynecol. 2013 Feb 21. pii: S0002-9378(13)00226-3. doi:
10.1016/j.ajog.2013.02.031. [Epub ahead of print]

More Research, More Responsibility: The Expansion of Duty to Warn in Cancer
Patients Considering Fertility Preservation.

Quinn GP, Vadaparampil ST.

Moffitt Cancer Center, Department of Health Outcomes and Behavior; University of
South Florida, Department of Oncologic Science. Electronic address:
Gwen.quinn@moffitt.org.

Reproductive technology is advancing at a steadfast pace. Researchers are
successfully refining options for fertility preservation, to the benefit of the
cancer community. Research has consistently shown cancer patients and survivors
desire to have risks to fertility and preservation options disclosed, and major
campaigns have been undertaken to refer these patients to fertility specialists.
However, the decision to pursue fertility preservation is not an isolated
judgment. A variety of future decisions may arise for the individual or couple,
choices that may not have been relayed during the initial decision-making
process. Future decisions include the length of time to continue to store frozen
gametes, donating banked gametes to infertile couples, and whether embryos
created with one partner would be accepted by a new partner. It is important to
continue the advancement of fertility preservation not only in the scientific
milieu, but also in addressing a patient's preparedness for long-term decision
making.

Copyright © 2013 Mosby, Inc. All rights reserved.

PMID: 23439324  [PubMed – as supplied by publisher]

5. Fertil Steril. 2013 Feb 20. pii: S0015-0282(13)00214-8. doi:
10.1016/j.fertnstert.2013.01.141. [Epub ahead of print]

In vitro maturation of human immature oocytes for fertility preservation.

Chian RC, Uzelac PS, Nargund G.

State Key Laboratory for Reproductive Medicine, Nanjing Medical University,
Nanjing, People's Republic of China; Department of Obstetrics and Gynecology,
McGill University, Montreal, Quebec, Canada. Electronic address:
ri-cheng.chian@mcgill.ca.

Cryopreservation of embryos, oocytes, or ovarian tissues is the main option for
female fertility preservation. Oocyte cryopreservation has emerged as especially
important: the dramatic increase in the number of infants born from vitrified
oocytes indicates that it is becoming one of the most important intervention
options. However, oocyte cryopreservation with standard controlled ovarian
hyperstimulation may not be feasible for some cancer patients as there are
serious concerns about the effect of ovarian stimulation with hormones on the
risk of cancer recurrence. Also, urgent gonadotoxic cancer treatment may not
allow sufficient time for a patient to undergo hormonal ovarian stimulation.
Thus, immature oocyte retrieval from ovaries without ovarian stimulation followed
by in vitro maturation and vitrification is a promising fertility preservation
option for women who cannot undergo ovarian stimulation or cannot delay their
gonadotoxic cancer treatment. Immature oocytes can be collected from the ovaries
during both the follicular and luteal phases, which maximizes the possibility for
fertility preservation. The combination of ovarian tissue cryopreservation with
immature oocyte collection from the tissue followed by oocyte vitrification via
in vitro maturation represents another promising approach of fertility
preservation in young women with cancer.

Copyright © 2013 American Society for Reproductive Medicine. Published by
Elsevier Inc. All rights reserved.

PMID: 23433515  [PubMed – as supplied by publisher]

6. Am J Bioeth. 2013 Mar;13(3):28-35. doi: 10.1080/15265161.2012.760672.

Expanding access to testicular tissue cryopreservation: an analysis by analogy.

Ruutiainen T, Miller S, Caplan A, Ginsberg JP.

a Tulane University School of Medicine.

Researchers are developing a fertility preservation technique-testicular tissue
cryopreservation (TTCP)-for prepubescent boys who may become infertile as a
result of their cancer treatment. Although this technique is still in
development, some researchers are calling for its widespread use. They argue that
if boys do not bank their tissue now, they will be unable to benefit from any
therapies that might be developed in the future. There are, however, risks
involved with increasing access to an investigational procedure. This article
examines four methods of expanding access to TTCP: (1) expansion of institutional
review board (IRB)-approved research trials; (2) offering TTCP as an innovative
procedure in hospitals; (3) offering TTCP as a standard practice in hospitals;
and (4) commercialization of TTCP. The ethical and practical implications of each
are evaluated through a comparison with umbilical cord blood banking (UCBB), a
technology that has achieved widespread use based on similar claims of future
benefit.

PMID: 23428034  [PubMed – in process]

7. Hum Reprod. 2013 Feb 20. [Epub ahead of print]

Spermatogonial stem cell preservation and transplantation: from research to
clinic.

Goossens E, Van Saen D, Tournaye H.

Biology of the testis (BITE), Department for Embryology and Genetics, Vrije
Universiteit Brussel (VUB), Laarbeeklaan 103, Brussels 1090, Belgium.

STUDY QUESTION: What issues remain to be solved before fertility preservation and
transplantation can be offered to prepubertal boys? SUMMARY ANSWER: The main
issues that need further investigation are malignant cell decontamination,
improvement of in vivo fertility restoration and in vitro maturation. WHAT IS
KNOWN ALREADY: Prepubertal boys who need gonadotoxic treatment might render
sterile for the rest of their life. As these boys do not yet produce sperm cells,
they cannot benefit from sperm banking. Spermatogonial stem cell (SSC) banking
followed by autologous transplantation has been proposed as a fertility
preservation strategy. But before this technique can be applied in the clinic,
some important issues have to be resolved. STUDY DESIGN, SIZE DURATION: Original
articles as well as review articles published in English were included in a
search of the literature. PARTICIPANTS/MATERIALS, SETTING, METHODS: Relevant
studies were selected by an extensive Medline search. Search terms were fertility
preservation, cryopreservation, prepubertal, SSC, testis tissue, transplantation,
grafting and in vitro spermatogenesis. The final number of studies selected for
this review was 102. MAIN RESULTS AND THE ROLE OF CHANCE: Cryopreservation
protocols for testicular tissue have been developed and are already being used in
the clinic. Since the efficiency and safety of SSC transplantation have been
reported in mice, transplantation methods are now being adapted to the human
testes. Very recently, a few publications reported on in vitro spermatogenesis in
mice, but this technique is still far from being applied in a clinical setting.
LIMITATIONS, REASONS FOR CAUTION: Using tissue from cancer patients holds a
potential risk for contamination of the collected testicular tissue. Therefore,
it is of immense importance to separate malignant cells from the cell suspension
before transplantation. Because biopsies obtained from young boys are small and
contain only few SSCs, propagation of these cells in vitro will be necessary.
WIDER IMPLICATIONS OF THE FINDINGS: The ultimate use of the banked tissue will
depend on the patient's disease. If the patient was suffering from a
non-malignant disease, tissue grafting might be offered. In cancer patients,
decontaminated cell suspensions will be injected in the testis. For patients with
Klinefelter syndrome, the only option would be in vitro spermatogenesis. However,
at present, restoring fertility in cancer and Klinefelter patients is not yet
possible. STUDY FUNDING/COMPETING INTEREST(S): Research Foundation, Flanders
(G.0385.08 to H.T.), the Institute for the Agency for Innovation, Belgium
(IWT/SB/111245 to E.G.), the Flemish League against Cancer (to E.G.), Kom op
tegen kanker (G.0547.11 to H.T.) and the Fund Willy Gepts (to HT). E.G. is a
Postdoctoral Fellow of the FWO, Research Foundation, Flanders. There are no
conflicts of interest.

PMID: 23427228  [PubMed – as supplied by publisher]

8. Eur J Surg Oncol. 2013 Feb 16. pii: S0748-7983(13)00248-5. doi:
10.1016/j.ejso.2013.02.004. [Epub ahead of print]

Preservation of the internal genital organs during radical cystectomy in selected
women with bladder cancer: A report on 15 cases with long term follow-up.

Ali-El-Dein B, Mosbah A, Osman Y, El-Tabey N, Abdel-Latif M, Eraky I, Shaaban AA.

Urology Department, Urology and Nephrology Center, Faculty of Medicine, Mansoura
University, Mansoura 35516, Egypt. Electronic address: balieldein@yahoo.com.

PURPOSE: To prospectively present the technique, functional and oncological
outcome of internal genitalia sparing cystectomy for bladder cancer in 15
selected women. PATIENTS AND METHODS: Between January 1995 and December 2010, 305
women underwent orthotopic neobladder after radical cystectomy. Of these, 15
cases with a mean age of 42 years underwent genitalia sparing. Inclusion criteria
included stage (T2b N0 Mo or less, as assessed preoperatively, unifocal tumors
away from the trigone, sexually active young women and internal genitalia free of
tumor. Cystectomy with preservation of the uterus, vagina and ovaries and
Hautmann neobladder were performed. Oncological, functional, urodynamic and
sexual outcome using Female Sexual Function Index (FSFI) were evaluated. RESULTS:
Definitive histopathology showed advanced stage not recognized preoperatively in
2 patients, who developed local recurrence and bony metastasis after 3-4 months.
A third patient developed bony metastasis after 15 months. No recurrence
developed in the retained genital organs. The remaining 12 patients remained free
of disease with a mean follow-up of 70 months. Among women eligible for
functional evaluation, daytime and nighttime continence were achieved in 13/13
(100%) and 12/13 (92)%, respectively. Chronic urinary retention was not noted.
The urodynamic parameters were comparable to those in other patients without
genital preservation. Sexual function (FSFI) was better in these patients than in
others without genital preservation. CONCLUSIONS: Genital sparing cystectomy for
bladder cancer is feasible in selected women. It provides a good functional
outcome, better sexual function and the potential for fertility preservation. So
far, the oncological outcome is favorable.

Copyright © 2013 Elsevier Ltd. All rights reserved.

PMID: 23422323  [PubMed – as supplied by publisher]

9. Chin Med J (Engl). 2013 Feb;126(4):688-91.

Gonadotropin-releasing hormone agonists cotreatment during chemotherapy in
borderline ovarian tumor and ovarian cancer patients.

Zhu HL, Wang Y, Li XP, Wang CH, Wang Y, Cui H, Wang JL, Wei LH.

Department of Obstetrics and Gynecology, Peking University People's Hospital,
Beijing 100044, China.

BACKGROUND: Recently, conservative surgery is acceptable in young patients with
borderline ovarian tumor and ovarian cancer. The preservation of these patients'
future fertility has been the focus of recent interest. This study aimed to
observe the effect of gonadotropin-releasing hormone agonists (GnRHa) cotreatment
during chemotherapy in borderline ovarian tumor and ovarian cancer patients.
METHODS: Sixteen patients who were treated with fertility preservation surgery
for borderline ovarian tumor and ovarian cancer and then administered GnRHa
during chemotherapy in Peking University People's Hospital from January 2006 to
July 2010 were retrospectively analyzed. This group was compared with a control
group of 16 women who were treated concurrently with similar chemotherapy (n = 5)
without GnRHa or were historical controls (n = 11). The disease recurrence, the
menstruation status and reproductive outcome were followed up and compared
between the two groups.
RESULTS: There were no significant differences between both groups regarding age,
body weight, height, marriage status, classification of the tumors, stage of the
disease, as were the cumulative doses of each chemotherapeutic agent. One (1/16)
patient in the study group while 2 (2/16) patients in the control group relapsed
2 years after conclusion of the primary treatment (P > 0.05). All of the 16 women
in the study group compared with 11 of the 16 patients in the control group
resumed normal menses 6 months after the termination of the treatment (P < 0.05).
There were 4 spontaneous pregnancies in the study group while 2 in the control
group, all of the neonates were healthy.
CONCLUSIONS: GnRHa administration before and during chemotherapy in borderline
ovarian tumor and ovarian cancer patients who had undergone fertility
preservation operation may bring up higher rates of spontaneous resumption of
menses and a better pregnancy rate. Long-term follow up and large scale clinical
studies are required.

PMID: 23422190  [PubMed – in process]

10. Bone Marrow Transplant. 2013 Feb 18. doi: 10.1038/bmt.2013.13. [Epub ahead of
print]

Physician perceptions and practice patterns regarding fertility preservation in
hematopoietic cell transplant recipients.

Loren AW, Brazauskas R, Chow EJ, Gilleece M, Halter J, Jacobsohn DA, Joshi S,
Pidala J, Quinn GP, Wang Z, Apperley JF, Burns LJ, Hale GA, Hayes-Lattin BM,
Kamble R, Lazarus H, McCarthy PL, Reddy V, Warwick AB, Bolwell BJ, Duncan C,
Socie G, Sorror ML, Wingard JR, Majhail NS.

Abramson Cancer Center University of Pennsylvania Medical Center, Philadelphia,
PA, USA.

Physician practice variation may be a barrier to informing hematopoietic cell
transplant (HCT) recipients about fertility preservation (FP) options. We
surveyed HCT physicians in the United States to evaluate FP knowledge, practices,
perceptions and barriers. Of the 1035 physicians invited, 185 completed a 29-item
web-survey. Most respondents demonstrated knowledge of FP issues and discussed
and felt comfortable discussing FP. However, only 55% referred patients to an
infertility specialist. Most did not provide educational materials to patients
and only 35% felt that available materials were relevant for HCT. Notable
barriers to discussing FP included perception that patients were too ill to delay
transplant (63%), patients were already infertile from prior therapy (92%) and
time constraints (41%). Pediatric HCT physicians and physicians with access to an
infertility specialist were more likely to discuss FP and to discuss FP even when
prognosis was poor. On analyses that considered physician demographics, knowledge
and perceptions as predictors of referral for FP, access to an infertility
specialist and belief that patients were interested in FP were observed to be
significant. We highlight variation in HCT physician perceptions and practices
regarding FP. Physicians are generally interested in discussing fertility issues
with their patients but lack educational materials.Bone Marrow Transplantation
advance online publication, 18 February 2013; doi:10.1038/bmt.2013.13.

PMID: 23419436  [PubMed – as supplied by publisher]

11. Int J Dev Biol. 2012;56(10-11-12):919-929.

The use of immature oocytes in the fertility preservation of cancer patients:
current promises and challenges.

Combelles CM, Chateau G.

Middlebury College, Biology Department, Middlebury, VT, USA.
ccombell@middlebury.edu.

Improved oncological treatments permit increased survival rates, although cancer
patients remain at risk of losing ovarian function. An attractive option for
fertility preservation includes the use of immature oocytes, a strategy which can
occur on a rapid timeline and without hormonal stimulation. As a result, cancer
therapy can proceed promptly even in patients with hormone-sensitive tumors.
Following retrieval, immature oocytes can be cryopreserved at either the immature
germinal vesicle or the mature metaphase-II stage, i.e. either before or after in
vitro maturation (IVM). We present a critical review of previous human studies on
the cryopreservation of immature oocytes. Evaluations include in vitro
developmental com-petence upon thawing/warming, or organization of the spindle
and chromosomes. Reported successes vary, perhaps in relation to the source of
the oocytes and protocols for cryopreser-vation and IVM. Weaknesses exist with
the experimental designs implemented to date, so cau-tion must be exercised
before considering the use of immature oocytes to be a safe and reliable practice
in the fertility preservation of cancer patients. To date, results indicate that
with current protocols, it may be best to cryopreserve immature oocytes after IVM
at the metaphase-II stage. Nonetheless, efficacy remains very low. Future efforts
should tailor and optimize not only cryo-preservation, but also IVM protocols for
use in either germinal vesicle or metaphase-II oocytes, together with a
comprehensive assessment of oocyte function and developmental competence to term.
Despite current challenges, the burgeoning field of immature oocyte
cryopreservation constitutes a promising option for cancer patients with impaired
ovarian function.

PMID: 23417414  [PubMed – as supplied by publisher]

12. Int J Dev Biol. 2012;56(10-11-12):901-907.

Strategies to support human oocyte development in vitro.

Telfer EE, McLaughlin M.

Institute of Cell Biology and Centre for Integrative Physiology, University of
Edinburgh, Scotland. evelyn.telfer@ed.ac.uk.

Many young cancer patients are now being given the option to store ovarian
cortical biopsies before undergoing potentially damaging chemo or radio-therapy.
This tissue mainly contains large numbers of immature primordial follicles.
Currently the only option to restore fertility using this tissue is by
transplantation which may not be a viable option for all patients. Greater
options to realise the potential of this tissue to restore fertility could be
achieved by the development of in vitro systems that support oocyte development.
The ability to develop human oocytes from the most immature stages of follicles
(primordial) through to maturation and fertilisation in vitro would revolutionise
fertility preservation practice. This has been achieved in mouse where in vitro
grown (IVG) oocytes from primordial follicles have resulted in the production of
live offspring. However, developing IVG systems to support complete development
of human oocytes has been more difficult because of differences in scale of
timing and size. Our lab has been working on a multi-step culture system to
support growth and development of bo-vine and human oocytes from primordial
through to fully grown, using fresh and cryopreserved ovarian cortical tissue.
This review outlines the approaches being taken to obtain complete in vitro
development of human oocytes and strategies for assessing the health and
viability of IVG oocytes.

PMID: 23417412  [PubMed – as supplied by publisher]

13. J Assist Reprod Genet. 2013 Feb;30(2):203-6. doi: 10.1007/s10815-013-9947-7.

Ovarian stimulation protocols for onco-fertilty patients.

Koch J, Ledger W.

Obstetrics and Gynaecology, Department of Obstetrics and Gynaecology, University
of New South Wales, Royal Hospital for Women, Randwick, Sydney, Australia, NSW,
2031.

PURPOSE: To review options for ovarian stimulation before oocyte collection for
fertility preservation for women with cancer or related diseases who require
potentially sterilizing chemo- or radiotherapy.
METHODS: Narrative review of current practice.
RESULTS: Vitrification of oocytes and embryos has improved chances of pregnancy
for this group of patients in recent years, increasing the uptake of fertility
preservation before cancer treatment substantially. Strategies for ovarian
stimulation for such patients should optimize oocyte yield whilst avoiding risk
of ovarian hyperstimulation.
CONCLUSIONS: Best practice in ovarian stimulation can deliver good numbers of
oocytes or embryos for cryopreservation with minimal risk of ovarian
hyperstimulation for women under 36 years of age. Results are less encouraging
for older patients.

PMID: 23417355  [PubMed – in process]

14. J Assist Reprod Genet. 2013 Feb 16. [Epub ahead of print]

A review of 15 years of ovarian tissue bank activities.

Dolmans MM, Jadoul P, Gilliaux S, Amorim CA, Luyckx V, Squifflet J, Donnez J, Van
Langendonckt A.

Department of Gynecology, Institut de Recherche Expérimentale et Clinique (IREC),
Université Catholique de Louvain, Avenue Mounier, 52, B-1200, Brussels, Belgium,
marie-madeleine.dolmans@uclouvain.be.

PURPOSE: To review 15 years of activities in ovarian tissue cryobanking from
medical database files, including patient indications, histological evaluation
and clinical characteristics. METHODS: Retrospective longitudinal analysis of
data from an ovarian tissue bank in an academic hospital. Five hundred and
eighty-two patients had their ovarian tissue cryobanked between April 1997 and
January 2012. Analysis of cryobanking database: precryopreservation patient
characteristics, indications and safety issues, laboratory files and
postcryopreservation clinical data. RESULTS: Of the 582 patients who had their
ovarian tissue cryopreserved, 106 patients donated for research purposes and 476
patients for fertility preservation and long-term cryopreservation. Clinical data
analysis of the 476 patients revealed a mean age at the time of cryopreservation
of 23 ± 8.5 years (range: 9 months – 39 years), with 96.2 % of subjects aged
≤35 years (n = 458). Among 391 cases of malignant disease, hematological
malignancies (39.9 %, n = 156) and breast cancer (21.7 %, n = 85) were the two
main indications. At histology, malignant cells were found in ovarian tissue from
leukemia patients (n = 3) and non-Hodgkin's lymphoma patients (n = 2). Eleven
patients underwent autotransplantation, resulting in 5 live births and 1 ongoing
pregnancy. CONCLUSION: This is the largest and most comprehensive study to
describe and analyze indications and clinical patient characteristics before and
after ovarian tissue cryopreservation. The procedure is safe, easy and promising.
The database concept is a useful tool in patient selection for
autotransplantation.

PMID: 23417329  [PubMed – as supplied by publisher]

15. Reprod Biomed Online. 2013 Jan 19. pii: S1472-6483(13)00011-4. doi:
10.1016/j.rbmo.2013.01.003. [Epub ahead of print]

Response to ovarian stimulation in patients facing gonadotoxic therapy.

Johnson LN, Dillon KE, Sammel MD, Efymow BL, Mainigi MA, Dokras A, Gracia CR.

Reproductive Endocrinology and Infertility, University of Pennsylvania, 3701
Market St, Ste 800, Philadelphia, PA 19104, United States. Electronic address:
Lauren.johnson2@uphs.upenn.edu.

Chemotherapy naïve patients undergoing embryo/oocyte banking for fertility
preservation (FP) were assessed for response to ovarian stimulation. Fifty FP
patients facing gonadotoxic therapy were matched by age, race, cycle number, date
of stimulation and fertilization method to patients undergoing IVF for
infertility or oocyte donation. There were no differences in baseline FSH,
anti-Müllerian hormone, antral follicle count and total gonadotrophin dose. FP
patients had more immature oocytes (2.2 versus 1.1; P=0.03) and lower
fertilization rates per oocyte retrieved (52% versus 70%; P=0.002). There were no
differences in numbers of oocytes retrieved, mature oocytes or fertilized
embryos. Subgroup analysis revealed that FP patients taking letrozole required
higher gonadotrophin doses (3077IU versus 2259IU; P=0.0477) and had more immature
oocytes (3.4 versus 1.2; P=0.03) than matched controls. There were no differences
in gonadotrophin dose or oocyte immaturity among FP patients not taking
letrozole. Overall, chemotherapy naïve FP patients had similar ovarian reserve,
response to stimulation and oocyte and embryo yield compared to controls.
Patients who received letrozole required higher gonadotrophin doses and produced
more immature oocytes, suggesting that response to ovarian stimulation may be
impaired in patients with hormone-sensitive cancers receiving letrozole. With
improvement in cancer survival rates, there has been a shift in attention toward
management of long-term consequences of cancer therapy, including infertility.
Many young women with cancer, particularly those who will be treated with
chemotherapy, pursue fertility preservation (FP) strategies for the purpose of
banking oocytes or embryos for future use. We examined patients with no prior
exposure to chemotherapy who underwent IVF to freeze embryos or oocytes for FP.
Fifty FP patients were identified and matched to healthy controls by age, race,
cycle number, date of stimulation and fertilization method. There were no
differences in baseline measures of ovarian reserve or amount of medication
needed to stimulate the ovaries. FP patients had more immature oocytes and lower
fertilization rates than controls. There were no differences in number of oocytes
retrieved, number of mature oocytes, rate of maturity or number of fertilized
embryos. Subgroup analysis revealed that FP patients taking letrozole required
higher gonadotrophin doses and had more immature oocytes compared with matched
controls. There were no differences in gonadotrophin dose or oocyte immaturity
among FP patients not taking letrozole. We demonstrated that FP patients not
previously exposed to chemotherapy have similar ovarian reserve, response to
stimulation and oocyte and embryo yield compared with infertile and donor
controls. Patients who received letrozole required higher gonadotrophin doses and
produced more immature oocytes, suggesting that response to ovarian stimulation
may be impaired in patients with hormone-sensitive cancers receiving letrozole.

Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All
rights reserved.

PMID: 23415997  [PubMed – as supplied by publisher]

16. Cancer Invest. 2013 Feb 14. [Epub ahead of print]

Fertility Preservation in Young Women with Cervical Cancer: An Oncologic Dilemma
or a New Conception of Fertility Sparing Surgery?

Gizzo S, Ancona E, Patrelli TS, Saccardi C, Anis O, Donato D, Nardelli GB.

Department of Woman and Child Health, University of Padua , Padua , Italy1.

PMID: 23410239  [PubMed – as supplied by publisher]

17. J Sex Med. 2013 Feb;10 Suppl 1:21-34. doi: 10.1111/jsm.12002.

The physical consequences of gynecologic cancer surgery and their impact on
sexual, emotional, and quality of life issues.

Carter J, Stabile C, Gunn A, Sonoda Y.

Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer
Center, New York, NY, USA Department of Psychiatry and Behavioral Sciences,
Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

Introduction.  Surgical management of gynecologic cancer can cause short- and
long-term effects on sexuality, reproductive function, and overall quality of
life (QOL) (e.g., sexual dysfunction, infertility, lymphedema). However,
innovative approaches developed over the past several decades have improved
oncologic outcomes and reduced treatment sequelae. Aim.  To provide an overview
of the standards of care and major advancements in gynecologic cancer surgery,
with a focus on their direct physical impact, as well as emotional, sexual, and
QOL issues. This overview will aid researchers and clinicians in the
conceptualization of future clinical care strategies and interventions to improve
sexual/vaginal/reproductive health and QOL in gynecologic cancer patients. Main
Outcome Measures.  Comprehensive overview of the literature on gynecologic
oncology surgery. Methods.  Conceptual framework for this overview follows the
current standards of care and recent surgical approaches to treat gynecologic
cancer, with a brief overview describing primary management objectives and the
physical, sexual, and emotional impact on patients. Extensive literature support
is provided. Results.  The type and radicality of surgical treatment for
gynecologic cancer can influence sexual function and play a significant role in
QOL. Psychological, sexual, and QOL outcomes improve as surgical procedures
continue to evolve. Procedures for fertility preservation, laparoscopy, sentinel
lymph node mapping, and robotic and risk-reducing surgery have advanced the field
while reducing treatment sequelae. Nevertheless, interventions that address
sexual and vaginal health issues are limited. Conclusions.  It is imperative to
consider QOL and sexuality during the treatment decision-making process. New
advances in detection and treatment exist; however, psycho-educational
interventions and greater patient-physician communication to address sexual and
vaginal health concerns are warranted. Large, prospective clinical trials
including patient-reported outcomes are needed in gynecologic oncology
populations to identify subgroups at risk. Future study designs need clearly
defined samples to gain insight about sexual morbidity and foster the development
of targeted interventions. Carter J, Stabile C, Gunn A, and Sonoda Y. The
physical consequences of gynecologic cancer surgery and their impact on sexual,
emotional, and quality of life issues. J Sex Med 2013;10(suppl 1):21-34.

© 2013 International Society for Sexual Medicine.

PMID: 23387909  [PubMed – in process]

18. Reprod Domest Anim. 2012 Dec;47 Suppl 6:261-5. doi: 10.1111/rda.12010.

On the horizon for fertility preservation in domestic and wild carnivores.

Comizzoli P, Wildt DE.

Center for Species Survival, Smithsonian Conservation Biology Institute, National
Zoological Park, Washington, DC 20008, USA. comizzolip@si.edu

Innovations are emerging from the growing field of fertility preservation for
humans and laboratory animals that are relevant to protecting and propagating
valuable domestic and wild carnivores. These extend beyond the 'classical'
approaches associated with sperm, oocyte and embryo freezing to include gonadal
tissue preservation combined with in vitro culture or xenografting, all of which
have potential for rescuing vast amounts of unused and wasted germplasm. Here, we
review approaches under development and predicted to have applied value within
the next decade, including the following: (i) direct use of early-stage gametes
for in vitro fertilization; (ii) generation of more mature gametes from gonadal
tissue or stem cells; (iii) simplification, enhanced safety and efficacy of
cryopreservation methods; and (iv) biostabilization of living cells and tissues
at ambient temperatures. We believe that all of these fertility preservation
strategies will offer knowledge and tools to better manage carnivores that serve
as human companions, valuable biomedical models or require assistance to reverse
endangerment.

Published 2012. This article is a U.S. Government work and is in the public
domain in the USA.

PMCID: PMC3576725 [Available on 2013/12/1] PMID: 23279514  [PubMed – in process]

19. Gynecol Obstet Invest. 2013 Feb 6. [Epub ahead of print]

Ovarian Tissue Cryopreservation by Vitrification in Olive Baboons (Papio Anubis)
: A Pilot Study.

Nyachieo A, Spiessens C, Chai DC, Kiulia NM, Willemen D, Mwenda JM, Bourgain C,
D'Hooghe TM.

Leuven University Fertility Centre, Leuven, Belgium.

Background: Ovarian tissue cryopreservation by vitrification is an attractive
technique for fertility preservation in women. However, this technique has not
been optimized. The aim of this study was to evaluate the baboon as a model for
the preclinical study of ovarian tissue cryopreservation by vitrification and
thawing. Methods: Ovarian cortical tissues (1-mm cubes) were obtained surgically
from adult female olive baboons (n = 9) maintained in captivity and vitrified
using dimethyl sulphoxide and ethylene glycol protocol. The proportion of
morphologically intact follicles (primordial, primary and secondary) in paired
fresh and cryopreserved (vitrified-thawed) ovarian tissues was compared. Results:
Overall, 67.1% of follicles were morphologically normal after vitrification. When
compared to fresh ovarian tissue, vitrified-thawed ovarian tissue contained a
comparable number of intact primordial follicles (48.9 vs. 52.9%), and a lower
number of both primary (14.8 vs. 29.5%; p < 0.05) and secondary (2.0 vs. 0.7%; p
< 0.05) follicles. Conclusion: After vitrification and thawing, baboon ovarian
tissue retains about 67% of morphologically normal follicles, which is comparable
to results for human ovarian tissue, and suggests that the olive baboon is a
promising animal model for preclinical assessment of ovarian vitrification,
thawing and autotransplantation studies.

Copyright © 2013 S. Karger AG, Basel.

PMID: 23391858  [PubMed – as supplied by publisher]

20. J Assist Reprod Genet. 2013 Feb;30(2):213-9. doi: 10.1007/s10815-013-9944-x.

Progress in understanding human ovarian folliculogenesis and its implications in
assisted reproduction.

Yang DZ, Yang W, Li Y, He Z.

Department of Obstetrics & Gynecology, Memorial Hospital, Sun Yat-Sen University,
No. 107, Yanjiang Rd, Guangzhou, 510120, China, yangdz@mail.sysu.edu.cn.

PURPOSE: To highlight recent progress in understanding the pattern of follicular
wave emergence of human menstrual cycle, providing a brief overview of the new
options for human ovarian stimulation and oocyte retrieval by making full use of
follicular physiological waves of the patients either with normal or abnormal
ovarian reserve.
METHODS: Literature review and editorial commentary.
RESULTS: There has been increasing evidence to suggest that multiple (two or
three) antral follicular waves are recruited during human menstrual cycle. The
treatment regimens designed based on the theory of follicular waves, to promote
increased success with assisted reproduction technology (ART) and fertility
preservation have been reported. These new options for human ovarian stimulation
and oocyte retrieval by making full use of follicular waves of the patients
either with normal or abnormal ovarian reserve lead to new thinking about the
standard protocols in ART and challenge the traditional theory that a single wave
of antral follicles grows only during the follicular phase of the menstrual
cycle.
CONCLUSIONS: The understanding of human ovarian folliculogenesis may have
profound implications in ART and fertility preservation. Further studies are
needed to evaluate the optimal regimens in ART based on the theory of follicular
waves and to identify non-invasive markers for predicting the outcome and the
potential utilities of follicles obtained from anovulatory follicular waves in
ART.

PMID: 23388838  [PubMed – in process]

21. Am J Surg Pathol. 2013 Feb 5. [Epub ahead of print]

Ovarian Surface Epithelial Neoplasms in the Pediatric Population: Incidence,
Histologic Subtype, and Natural History.

Hazard FK, Longacre TA.

Departments of *Pathology †Pediatrics, Stanford University School of Medicine,
Stanford, CA.

Surface epithelial neoplasms account for a small but significant proportion of
pediatric ovarian tumors. The overall incidence, prevalence of histologic
subtypes, and natural history of these neoplasms has not been thoroughly
evaluated. A retrospective review of the pathology archives of Stanford
University School of Medicine yielded 69 surface epithelial ovarian tumors in 64
pediatric patients 18 years of age or younger from 1974 to 2010. Tumors comprised
benign (57.8%), borderline/low malignant potential (LMP) (37.5%), and malignant
(4.7%) subgroups and exhibited serous, mucinous, and mixed histology; there were
no clear cell, pure endometrioid, or transitional (Brenner) tumors. In addition,
no high-grade carcinomas were identified. Clinical follow-up data were available
in a subset of patients (maximum follow-up, 22 y). Similar numbers of recurrences
were found in each of the 3 subgroups. However, overall survival was 100% for
benign and borderline/LMP tumors and 50% for carcinomas. The type of surgical
management and the use of chemotherapy varied; 2 patients with borderline/LMP
tumors were treated by sterilizing procedures and/or chemotherapy. These data
suggest that surface epithelial neoplasms comprise a small but significant
proportion of ovarian tumors in the pediatric population, and they exhibit a
marked preponderance for benign, borderline, and low-grade malignant subgroups.
In contrast to their adult counterpart, high-grade serous carcinoma in children
is extraordinarily rare and not seen in this series. Given this difference,
uniform treatment modalities with consideration for ovarian conservation and
fertility preservation should be rigorously adopted in any pediatric patient with
a suspected ovarian surface epithelial neoplasm.

PMID: 23388124  [PubMed – as supplied by publisher]

22. J Clin Oncol. 2013 Feb 4. [Epub ahead of print]

Female Reproductive Health After Childhood, Adolescent, and Young Adult Cancers:
Guidelines for the Assessment and Management of Female Reproductive
Complications.

Metzger ML, Meacham LR, Patterson B, Casillas JS, Constine LS, Hijiya N, Kenney
LB, Leonard M, Lockart BA, Likes W, Green DM.

Monika L. Metzger and Daniel M. Green, St Jude Children's Research Hospital,
Memphis, TN; Monika L. Metzger and Wendy Likes, University of Tennessee, Memphis,
TN; Lillian R. Meacham and Briana Patterson, Emory University, Atlanta, GA;
Jacqueline S. Casillas, University of California at Los Angeles, Los Angeles, CA;
Louis S. Constine, University of Rochester, Rochester, NY; Nobuko Hijiya,
Northwestern University; Barbara A. Lockart, Ann and Robert H. Lurie Children's
Hospital of Chicago, Chicago, IL; Lisa B. Kenney, Dana-Farber Cancer Institute
and Children's Hospital Boston, Boston, MA; and Marcia Leonard, University of
Michigan, Ann Arbor, MI.

PURPOSEAs more young female patients with cancer survive their primary disease,
concerns about reproductive health related to primary therapy gain relevance.
Cancer therapy can often affect reproductive organs, leading to impaired pubertal
development, hormonal regulation, fertility, and sexual function, affecting
quality of life. METHODSThe Children's Oncology Group Long-Term Follow-Up
Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer
(COG-LTFU Guidelines) are evidence-based recommendations for screening and
management of late effects of therapeutic exposures. The guidelines are updated
every 2 years by a multidisciplinary panel based on current literature review and
expert consensus.ResultsThis review summarizes the current task force
recommendations for the assessment and management of female reproductive
complications after treatment for childhood, adolescent, and young adult cancers.
Experimental pretreatment as well as post-treatment fertility preservation
strategies, including barriers and ethical considerations, which are not included
in the COG-LTFU Guidelines, are also discussed. CONCLUSIONOngoing research will
continue to inform COG-LTFU Guideline recommendations for follow-up care of
female survivors of childhood cancer to improve their health and quality of life.

PMID: 23382474  [PubMed – as supplied by publisher]

23. Transplantation. 2013 Feb 15;95(3):426-433.

Isoform 111 of Vascular Endothelial Growth Factor (VEGF111) Improves Angiogenesis
of Ovarian Tissue Xenotransplantation.

Labied S, Delforge Y, Munaut C, Blacher S, Colige A, Delcombel R, Henry L,
Fransolet M, Jouan C, d'Hauterive SP, Noël A, Nisolle M, Foidart JM.

1 Laboratory of Tumor and Development Biology, Groupe Interdisciplinaire de
Génoprotéomique Appliqué (GIGA-R), Université de Liège, Liège, Belgium. 2
Laboratory of Connective Tissues Biology, Groupe Interdisciplinaire de
Génoprotéomique Appliqué (GIGA-R), Université de Liège, Liège, Belgium. 3
Department of Gynecology, Université de Liège, Liège, Belgium. 4 The CPMA
Department, Université de Liège, Liège, Belgium. 5 Address correspondence to:
Soraya Labied, Ph.D., Laboratory of Tumor and Development Biology, Université de
Liège, Tour de Pathologie (B23), Sart-Tilman, B-4000 Liège, Belgium.

BACKGROUND: Cryopreservation of cortex ovarian tissue before anticancer therapy
is a promising technique for fertility preservation mainly in children and young
women. Ischemia in the early stage after ovarian graft causes massive follicle
loss by apoptosis. VEGF111 is a recently described vascular endothelial growth
factor (VEGF) isoform that does not bind to the extracellular matrix, diffuses
extensively, and is resistant to proteolysis. These properties confer a
significantly higher angiogenic potential to VEGF111 in comparison with the other
VEGF isoforms. METHODS: We evaluated the morphology of cryopreserved sheep
ovarian cortex grafted in the presence or absence of VEGF111. Ovarian cortex
biopsies were embedded in type I collagen with or without VEGF111 addition before
transplantation to severe combined immunodeficient mice ovaries. Transplants were
retrieved 3 days or 3 weeks later. Follicular density, vasculature network,
hemoglobin content, and cell proliferation were analyzed. RESULTS: Addition of
VEGF111 increased density of functional capillaries (P=0.01) 3 days after
grafting. By double immunostaining of Ki-67 and von Willebrand factor, we
demonstrated that proliferating endothelial cells were found in 83% of the
VEGF111 group compared with 33% in the control group (P=0.001). This
angiostimulation was associated with a significant enhancement of hemoglobin
content (P=0.03). Three weeks after transplantation, the number of primary
follicles was significantly higher in VEGF111 grafts (P=0.02). CONCLUSION:
VEGF111 accelerates blood vessel recruitment and functional angiogenesis and
improves the viability of ovarian cortex by limiting ischemia and ovarian cortex
damage.

PMID: 23380862  [PubMed – as supplied by publisher]

24. Fertil Steril. 2013 Feb 1. pii: S0015-0282(13)00133-7. doi:
10.1016/j.fertnstert.2013.01.090. [Epub ahead of print]

In vitro maturation of oocytes: uncommon indications.

Grynberg M, El Hachem H, de Bantel A, Benard J, le Parco S, Fanchin R.

Service de Gynécologie-Obstétrique et Médecine de la Reproduction, Hôpital
Antoine Béclère, Clamart, Universite Paris-Sud, Clamart, France. Electronic
address: michael.grynberg@abc.aphp.fr.

Retrieval of immature oocytes from unstimulated ovaries, followed by in vitro
maturation (IVM) was initially proposed to avoid the risks and side effects of
exogenous gonadotropin administration. Therefore, during the past decades, IVM
was mainly offered to patients with polycystic ovary syndrome (PCOS) at high risk
of ovarian hyperstimulation syndrome (OHSS). However, the development of
fertility preservation has recently opened new perspectives in the field of IVM.
The present review summarizes uncommon indications of IVM, which is a viable
option to treat infertility in patients with ovarian resistance to FSH, but may
also be considered to preserve fertility in leukemia as well as before ovarian
transposition and endometrioma excision.

Copyright © 2013 American Society for Reproductive Medicine. Published by
Elsevier Inc. All rights reserved.

PMID: 23380185  [PubMed – as supplied by publisher]

25. Fertil Steril. 2013 Jan 29. pii: S0015-0282(12)02525-3. doi:
10.1016/j.fertnstert.2012.12.016. [Epub ahead of print]

Should we isolate human preantral follicles before or after cryopreservation of
ovarian tissue?

Vanacker J, Luyckx V, Amorim C, Dolmans MM, Van Langendonckt A, Donnez J, Camboni
A.

Pôle de Recherche en Gynécologie, Institut de Recherche Expérimentale et
Clinique, Université Catholique de Louvain, Brussels, Belgium.

OBJECTIVE: To evaluate the survival and growth potential of human preantral
follicles isolated before and after cryopreservation. DESIGN: Pilot study.
SETTING: Gynecology research unit in a university hospital. PATIENT(S): Six women
aged 27 to 32 years. INTERVENTION(S): Six ovarian biopsy samples were cut into
two equal parts, half subjected to slow-freezing followed by follicle isolation
(cryo-iso group) and alginate-matrigel embedding, and half immediately processed
for follicle isolation and alginate-matrigel embedding followed by slow-freezing
(iso-cryo group) or used as fresh controls (fresh group). MAIN OUTCOME
MEASURE(S): Follicle number, viability, diameter, and morphology. RESULT(S):
After 1,134 preantral follicles had been isolated from fresh biopsy samples and
1,132 from frozen specimens, the three groups were compared before and after 7
days of in vitro culture (IVC) in alginate-matrigel beads. No statistically
significant differences in viability were found between the three groups before
or after IVC, but follicle diameter increased in all three groups after IVC.
Morphology analysis revealed well-preserved follicles in both the iso-cryo and
cryo-iso groups after IVC. CONCLUSION(S): Human preantral follicles can be
successfully cryopreserved before or after isolation without impairing their
ability to survive and grow in vitro. This could lead to development of new
protocols for follicle cryopreservation, IVC, and grafting in clinical and
research settings for fertility preservation.

Copyright © 2013 American Society for Reproductive Medicine. Published by
Elsevier Inc. All rights reserved.

PMID: 23375199  [PubMed – as supplied by publisher]

26. J Fam Plann Reprod Health Care. 2013 Jan 30. [Epub ahead of print]

What to do now? How women with breast cancer make fertility preservation
decisions.

Snyder KA, Tate AL.

Lecturer, Department of Sociology, Northwestern University, Evanston, IL, USA.

OBJECTIVES: There has been increased attention paid to cancer-related infertility
and fertility preservation. However, how cancer patients decide whether or not to
pursue fertility preservation has not been fully examined. METHODS: The data come
from 34 interviews with women in the USA diagnosed with breast cancer prior to
40&emsp14;years of age who contemplated fertility preservation prior to cancer
treatment. Fully transcribed interviews were coded through a three-staged
inductive process. RESULTS: Three sets of factors that shaped the decision-making
process of the respondents regarding fertility preservation treatment options
were identified: perceived benefits (e.g. ability to use 'younger' eggs in the
future), inhibiting concerns (e.g. success rates) and influential relationships
(e.g. physicians, parents and partners). CONCLUSIONS: Respondents saw their main
fertility preservation decision as choosing whether or not to pursue egg/embryo
banking. The decision-making process was complicated and included both
health-related and personal considerations, with many respondents reporting a
lack of support services for fertility issues. Findings suggest that greater
attention needs to be placed on presenting patients with a wider range of
options. Those who counsel patients regarding fertility preservation decisions
should be aware of the influence of relationship dynamics, broader health care
concerns, and fertility histories on these decisions.

PMID: 23363470  [PubMed – as supplied by publisher]

27. Hum Reprod. 2013 Jan 29. [Epub ahead of print]

Genetic variation may modify ovarian reserve in female childhood cancer
survivors.

van Dorp W, van den Heuvel-Eibrink MM, Stolk L, Pieters R, Uitterlinden AG,
Visser JA, Laven JS.

Department of Paediatric Oncology/Haematology, ErasmusMC University Medical
Centre-Sophia's Children's Hospital Rotterdam, Dr Molewaterplein 60, 3015 GJ
Rotterdam, The Netherlands.

STUDY QUESTION: Are genetic polymorphisms, previously identified as being
associated with age at menopause in the healthy population, associated with
ovarian reserve and predicted age at menopause in adult long-term survivors of
childhood cancer? SUMMARY ANSWER: The CT genotype of rs1172822 in the BRSK1 gene
is associated with lower serum anti-Müllerian hormone (AMH) levels and a younger
predicted age at menopause in adult survivors of childhood cancer. WHAT IS KNOWN
ALREADY: Gonadotoxicity is a well-known late side effect of chemotherapy and
radiotherapy in adult survivors of childhood cancer. In the healthy population,
several genetic polymorphisms are associated with age at natural menopause.
Currently, data on the impact of previously identified variants in gene loci
associated with ovarian reserve in adult long-term survivors of childhood cancer
are lacking. STUDY DESIGN, SIZE, DURATION: We performed a pilot study in a
single-centre cohort of adult female Caucasian childhood cancer survivors (n =
176). PARTICIPANTS/MATERIALS, SETTING, METHODS: We determined serum AMH levels (a
marker of ovarian reserve) in adult survivors of childhood cancer (n = 176) and
studied single nucleotide polymorphisms (SNPs) previously reported to be
associated with age at natural menopause: BRSK1 (rs1172822), ARHGEF7 (rs7333181),
MCM8 (rs236114), PCSK1 (rs271924), IGF2R (rs9457827) and TNF (rs909253).
Association analysis was performed using the additive genetic model. Linear
regression was conducted to assess the effect of significant polymorphisms in two
previously published menopause prediction models. MAIN RESULTS AND THE ROLE OF
CHANCE: The CT genotype of rs1172822 in the BRSK1 (BR serine/threonine kinase 1)
gene was negatively associated with serum AMH levels in our cohort (odds ratio:
3.15, 95% confidence interval: 1.35-7.32, P = 0.008) and significantly associated
with the predicted age at menopause (P = 0.04). The other five SNPs were not
associated with serum AMH levels. LIMITATIONS, REASONS FOR CAUTION: This is a
pilot study showing preliminary data which must be confirmed. To confirm our
findings and enlarge the project, a nationwide genome-wide association (GWA)
project on the ovarian reserve in female survivors of childhood cancer should be
performed, including a replication cohort. WIDER IMPLICATIONS OF THE FINDINGS:
Our findings support the hypothesis that previously identified genetic
polymorphisms associated with age at menopause in healthy women may have an
effect on the onset of menopause in female survivors of childhood cancer. Our
study highlights a new aspect of the influences on the ovarian reserve after
childhood cancer, which should be investigated further in a nationwide GWA study.
Eventually, this information can help us to improve counselling on fertility
preservation prior to cancer treatment based on genetic factors in individual
patients. STUDY FUNDING AND CONFLICT OF INTEREST: W.D. is supported by the
Paediatric Oncology Centre Society for Research (KOCR), Rotterdam, The
Netherlands. J.S.E.L. has received fees and grant support from the following
companies (in alphabetic order): Ferring, Genovum, Merck-Serono, Organon,
Schering Plough and Serono. All other authors have nothing to disclose.

PMID: 23360674  [PubMed – as supplied by publisher]

28. J Chin Med Assoc. 2013 Feb;76(2):112-4. doi: 10.1016/j.jcma.2012.09.011. Epub
2012 Dec 28.

Treatment of ovarian endodermal sinus tumor to preserve fertility.

Chang YW, Chao KC, Sung PL, Li WH, Wang PH.

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital,
Taipei, Taiwan, ROC; Department of Obstetrics and Gynecology, National Yang-Ming
University School of Medicine, Taipei, Taiwan, ROC.

Endodermal sinus tumor, also known as yolk sac tumor (YST), is a malignant germ
cell tumor that most frequently occurs in the testis, the ovary, and
sacrococcygeal areas in children. YSTs are highly aggressive and because of the
early metastatic or invasive pattern, their prognosis has been poor. Treatment
methods for YSTs are usually intensive, including multiagent chemotherapy, and
have shown to improve patient survival significantly; therefore, it is important
to consider the reproductive function of these patients with long-term survival.
Herein, we present the case of a 31-year-old female, who was diagnosed with
unilateral ovarian YST at the age of 13. The patient was treated with
fertility-sparing surgery and postoperative adjuvant chemotherapy. During the
subsequent long-term follow-up, she was not only free of disease, but also had a
successful, naturally conceived pregnancy at 31 years of age. We, therefore,
conclude that YST is a curable disease, and that fertility-preservation surgery
and subsequent immediate combination chemotherapy is the treatment of choice.

Copyright © 2012. Published by Elsevier B.V.

PMID: 23351423  [PubMed – in process]

29. Gynecol Endocrinol. 2013 Jan 25. [Epub ahead of print]

Fertility preservation: current prospects and future challenges.

Wyns C.

Pôle de Recherche en Gynécologie, Institut de Recherche Expérimentale et Clinique
(IREC), Université Catholique de Louvain (UCL) , Brussels , Belgium , and.

Abstract Due to remarkable advances in cancer therapies, we have seen great
improvements in survival rates of pediatric and reproductive-age male patients.
Unfortunately, fertility in adult life might be severely impaired by these
treatments. Gonadotoxic therapy is also used to cure a variety of non-malignant
disorders. Providing young people undergoing gonadotoxic treatment with adequate
fertility preservation options is a challenging area of reproductive medicine and
merits broader diffusion in clinical practice. This paper, therefore, aims to
review current concepts and perspectives to restore fertility from germ cells or
gonadal tissue cryostored prior to gonadotoxic therapies in pre- and
post-pubertal patients. For patients rendered sterile after treatment, who did
not benefit from fertility preservation measures before therapy, the reproductive
potential of alternative sources of stem cells is also examined, although this is
at the research stage.

PMID: 23350667  [PubMed – as supplied by publisher]

30. Gynecol Endocrinol. 2013 Jan 24. [Epub ahead of print]

Cancer and fertility preservation: Barcelona consensus meeting.

Martínez F, Devesa M, Coroleu B, Tur R, González C, Boada M, Solé M, Veiga A,
Barri PN.

Departamento de Obstetricia, Ginecología y Medicina de la Reproducción, Institut
Universitari Dexeus, Universitat Autònoma de Barcelona , Barcelona , Spain and.

Abstract Improvements in early diagnosis and treatment strategies in cancer
patients have enabled younger women with cancer to survive. In addition to the
stressful event of the diagnosis, patients with malignant diseases face the
potential loss of the opportunity to have children. Preservation of fertility has
become a challenging issue and it is still surrounded by controversies. On the
basis of available evidence, a group of experts reached a consensus regarding the
options for trying to preserve fertility in women with cancer: among established
methods, in postpubertal women, oocyte cryopreservation is the preferred option,
whereas ovarian tissue cryopreservation is the only possibility for prepubertal
girls. Combining several strategies on an individual basis may improve the
chances of success. Realistic information should be provided before any
intervention is initiated. Counseling should offer support for patients and
provide better care by understanding emotional needs, psychological predictors of
distress and methods of coping. Early referral to the fertility specialist is
essential as fertility preservation (FP) may improve quality of life in these
patients. The information summarized here is intended to help specialists
involved in the treatment of cancer and reproductive medicine to improve their
understanding of procedures available for FP in young cancer patients.

PMID: 23347067  [PubMed – as supplied by publisher]

31. Curr Obstet Gynecol Rep. 2012 Dec 1;1(4):153-158.

Ethical and Psychosocial Impact of Female Infertility.

Leyser-Whalen O, Temple JR, Phelps JY.

Department of Sociology and Anthropology, The University of Texas at El Paso, Old
Main Bldg., El Paso, TX 79968, USA.

This manuscript reviews research from the past year on the ethical and
psychosocial impact of infertility on women and men. We discuss several issues
surrounding ovarian stimulation, particularly high-order multiple births, egg
banking (especially for research purposes), and diminished ovarian reserve. We
also present recent work on distress and counseling, which includes greater
attention to subgroups of infertile women. More research on issues confronting
men has emerged recently, and we outline these with regard to their relationships
with infertile women, or as the infertility patient. Last, we outline some
ethical issues posed by newer procedures of fertility preservation and uterine
transplant.

PMCID: PMC3547399 [Available on 2013/12/1] PMID: 23336092  [PubMed]

32. Hum Reprod. 2013 Jan 18. [Epub ahead of print]

A prospective case series of women with estrogen receptor-positive breast cancer:
levels of tamoxifen metabolites in controlled ovarian stimulation with high-dose
tamoxifen.

Balkenende EM, Dahhan T, Linn SC, Jager NG, Beijnen JH, Goddijn M.

Centre for Reproductive Medicine, Department of Obstetrics and Gynecology,
Academic Medical Centre, PO Box 22660, 1100 DD Amsterdam, The Netherlands.

Controlled ovarian stimulation (COS) in women with estrogen receptor
(ER)-positive breast cancer is potentially harmful because of the increase in
serum estrogen levels. During COS for cryopreservation of oocytes or embryos,
these women may receive high doses of tamoxifen (60 mg) to modulate the ER and
prevent extra growth of estrogen responsive tumours during COS. However, it is
unknown whether adequate serum concentrations of endoxifen, the most important
metabolite of tamoxifen, can be reached. The aim of this study is to evaluate
whether the tamoxifen dose used in a tamoxifen-COS combined schedule for women
with ER-positive breast cancer is high enough to reach endoxifen levels that are
considered therapeutically effective to inhibit breast cancer growth. The four
women with ER-positive breast cancer who underwent COS for cryopreservation of
oocytes were prospectively studied at the Academic Medical Centre, Amsterdam, the
Netherlands. Throughout COS, blood samples were collected and tamoxifen and
endoxifen levels were determined by a validated high-performance liquid
chromatography tandem mass spectrometry assay. The four women with ER-positive
breast cancer underwent a total of five COS cycles, while additionally using
tamoxifen 60 mg daily. The tamoxifen and endoxifen levels showed a large
variability between the women, with endoxifen levels during the whole period of
ovarian stimulation varying between 3.96 and 41.0 ng/ml. The average number of
vitrified oocytes was 11 (5-14). Therapeutically effective endoxifen serum levels
can be reached when tamoxifen is used to counteract estrogen levels during COS
for fertility preservation, but not in all women. Large variations of tamoxifen
and endoxifen levels between the women were observed.

PMID: 23335608  [PubMed – as supplied by publisher]

33. Am J Med Genet C Semin Med Genet. 2013 Feb 15;163(1):16-26. doi:
10.1002/ajmg.c.31350. Epub 2013 Jan 18.

Endocrinological issues and hormonal manipulation in children and men with
Klinefelter syndrome.

Wosnitzer MS, Paduch DA.

Department of Urology, Weill Cornell Medical College, 525 East 68th Street, Starr
900, New York, NY 10065.

47, XXY or Klinefelter syndrome (KS), the most common chromosomal aberration in
males, is characterized by either absolute or relative hypogonadism with frequent
decline in serum testosterone (T) following the onset of puberty. Decreased T
levels are the result of testicular dysfunction with decrease in size of Leydig
cells, and loss of germs and Sertoli cells leading to tubular hyalinization.
Increase in estradiol results from over-expression of aromatase CYP19. Deficient
androgen production and observed varied response of end-organs to T leads to
delayed progression of puberty with decreased facial/body hair, poor muscle
development, osteoporosis, and gynecomastia. It is possible that hypogonadism and
excessive estradiol production contribute to emotional and social immaturity, and
specific learning disabilities in KS. Based on the authors' experience and
literature review, early fertility preservation and hormonal supplementation may
normalize pubertal development, prevent metabolic sequelae of hypogonadism, and
have a positive effect on academic and social development. No randomized clinical
trials are available studying the effects of T supplementation on reproductive or
cognitive issues in KS. Aggressive T supplementation (topical gel) and selective
use of aromatase inhibitors may be considered at the onset of puberty with
careful follow-up and titration to reach age-specific high-normal physiologic
serum values. The decision to institute hormonal therapy should be part of a
multidisciplinary approach including physical, speech, behavioral, and
occupational therapy. © 2013 Wiley Periodicals, Inc.

Copyright © 2013 Wiley Periodicals, Inc.

PMID: 23335092  [PubMed – in process]

34. Fertil Steril. 2012 Dec 11. pii: S0015-0282(12)02442-9. doi:
10.1016/j.fertnstert.2012.11.030. [Epub ahead of print]

Parental attitudes toward fertility preservation in boys with cancer: context of
different risk levels of infertility and success rates of fertility restoration.

Sadri-Ardekani H, Akhondi MM, Vossough P, Maleki H, Sedighnejad S, Kamali K,
Ghorbani B, van Wely M, van der Veen F, Repping S.

Reproductive Biotechnology Research Center, Avicenna Research Institute, The
Academic Center for Education, Culture and Research (ACECR), Tehran, Iran; Center
for Reproductive Medicine, Department of Obstetrics and Gynecology, Academic
Medical Center, University of Amsterdam, Amsterdam, the Netherlands. Electronic
address: hsadri@wakehealth.edu.

OBJECTIVE: To measure the parental attitudes toward fertility preservation in
boys with cancer. DESIGN: Retrospective cohort study. SETTING: Questionnaire
survey via regular mail. PATIENT(S): A total of 465 families whose sons were
already treated for cancer. INTERVENTION(S): The questionnaire was designed for
two groups based on child's age at the time of cancer diagnosis: <12 and ≥12
years old. MAIN OUTCOME MEASURE(S): Descriptive statistics regarding a positive
or negative attitude of parents toward fertility preservation options in the
context of different risk levels of infertility and success rates of fertility
restoration. RESULT(S): The response rate was 78%. Sixty-four percent of parents
of boys ≥12 years old would agree to store sperm obtained by masturbation and/or
electroejaculation, and 54% of parents of boys <12 years old would agree to store
a testicular biopsy. If the risk of infertility or the success rate of fertility
restoration were ≤20%, more than one-fourth of parents would still opt for
fertility preservation. CONCLUSION(S): All parents should be counseled about the
risks of infertility due to cancer treatment, because many parents want to
preserve their son's fertility even if the risk of becoming infertile or the
chances on fertility restoration are low.

Copyright © 2013 American Society for Reproductive Medicine. Published by
Elsevier Inc. All rights reserved.

PMID: 23332678  [PubMed – as supplied by publisher]

35. Rev Med Suisse. 2012 Dec 5;8(365):2335-6, 2338-9.

[Fertility preservation and cancer in the male].

[Article in French]

Leyvraz RC, Vaucher L, Primi MP.

Laboratoire d'andrologie et de biologie de la reproduction Maternité, CHUV, 1011
Lausanne. celine.leyvraz@chuv.ch

Improvement in cancer treatments resulted in an increased number of men surviving
cancer. Quality of life has become an important issue in these patients. Anti
cancer treatments might have transient or definitive harmful effects on male
fertility. Sperm cryoconservation is currently the only proven method to preserve
fertility in patients undergoing oncologic treatment. It should be proposed to
every patient at reproductive age before chemotherapy, radiotherapy or any
surgery involving reproductive tract. Despite low use rate, this simple method
could allow patients presenting infertility after treatment to father a child.

PMID: 23330233  [PubMed – in process]

36. ISRN Oncol. 2012;2012:817065. doi: 10.5402/2012/817065. Epub 2012 Dec 18.

Fertility-preserving surgery in patients with early stage cervical carcinoma.

Kardakis S.

Department of Obstetrics and Gynaecology, Oncologic Clinic, Västerås Hospital,
72212 Västerås, Sweden.

Fertility preservation is an important issue for patients in reproductive age
with early stage cervical cancer. In view of recent developments, our purpose was
to review and discuss available surgical alternatives. A literature search was
conducted using PUBMED, including papers between 1980 and December 2011. In
patients with stage IA1 cervical cancer, conization is a valid alternative.
Patients with stage IA2-IB1 disease can be conservatively treated by radical
trachelectomy. This is as well-established conservative approach and appears to
be safe and effective in allowing a high chance of conception. Prematurity is the
most serious issue in pregnancies following trachelectomy. Less invasive options
such as simple trachelectomy or conization seem to be feasible for stages
IA2-IB1, but more and better evidence is needed. Neoadjuvant therapy might allow
conservative surgery to be performed also in patients with more extensive
lesions. Ovarian transposition is important when adjuvant radiation is needed. In
conclusion, available literature shows that there are interesting
fertility-sparing treatment alternatives to the "golden standard" for the
management of early cervical cancer in young women.

PMCID: PMC3539444
PMID: 23320192  [PubMed]

37. Hum Reprod. 2013 Mar;28(3):578-89. doi: 10.1093/humrep/des455. Epub 2013 Jan 12.

Vitrification preserves proliferation capacity in human spermatogonia.

Poels J, Van Langendonckt A, Many MC, Wese FX, Wyns C.

Gynecology Unit, Medical School, Institut de Recherche Expérimentale et Clinique,
Université Catholique de Louvain, Avenue Mounier, 52, 1200 Brussels, Belgium.

STUDY QUESTION: Does vitrification of human immature testicular tissue (ITT) have
potential benefits for future fertility preservation? Does vitrification of human
ITT have potential benefits in an in vivo murine xenotransplantation model?
SUMMARY ANSWER: Vitrification is able to maintain proliferation capacity in
spermatogonial cells after 6 months of xenografting. WHAT IS KNOWN ALREADY:
Controlled slow-freezing is the procedure currently applied for ITT cryobanking
in clinical practice. Vitrification has been proposed as a promising technique
for long-term storage of ITT, with a view to preserving spermatogonial stem cells
(SSCs) for future fertility restoration in young boys suffering from cancer.
After vitrification of ITT, in vitro survival of SSCs was demonstrated, but their
functionality was not evaluated. STUDY DESIGN, SIZE, DURATION: Ten ITT pieces
issuing from 10 patients aged 2-12 years were used. Fragments of fresh tissue
(serving as controls) and fresh, frozen-thawed and vitrified-warmed testicular
pieces xenografted to the scrotum of nude mice for 6 months were compared.
MATERIALS, SETTING, METHODS: Upon graft removal, histological and
immunohistochemical analyses were performed to evaluate spermatogonia (SG)
(MAGE-A4), intratubular proliferation (Ki67), proliferating SG and Leydig cells
(3β-HSD). The entire piece of grafted tissue was assessed in each case. MAIN
RESULTS AND THE ROLE OF CHANCE: Seminiferous tubules showed good integrity after
cryopreservation and xenografting for 6 months in all three groups. Survival of
SG and their ability to proliferate was observed by immunohistochemistry in all
grafted groups. SG were able to initiate spermatogenesis, but blockage at the
pachytene stage was observed. The recovery rate of SG was 3.4 ± 3.8, 4.1 ± 7.3
and 7.3 ± 6.3%, respectively, for fresh, slow-frozen and vitrified-warmed tissue
after 6 months of xenografting. LIMITATIONS, REASONS FOR CAUTION: The study is
limited by the low availability of ITT samples of human origin. The mouse
xenotransplantation model needs to be refined to study human spermatogenesis.
WIDER IMPLICATIONS OF THE FINDINGS: The findings of the present study have
potential implications for cryobanking of ITT and fertility preservation.
Spermatogonial loss recorded after fresh ITT transplantation indicates that the
avascular grafting technique needs to be optimized. There are so far no
convincing data justifying modification of current clinical practice for ITT
storage with slow-freezing, but this study demonstrates that it is worth pursuing
optimization of ITT vitrification as an alternative for preservation of SSCs.
STUDY FUNDING/COMPETING INTEREST(S): The present study was supported by a grant
from the Fonds National de la Recherche Scientifique de Belgique (grant Télévie
N(°) 7. 4.572.09.F). The authors declare that there is no conflict of interest.

PMID: 23315062  [PubMed – in process]

38. J Natl Compr Canc Netw. 2013 Jan 1;11(1):71-7.

Optimizing fertility preservation practices for adolescent and young adult cancer
patients.

Johnson RH, Kroon L.

Seattle Children's Hospital, University of Washington, Seattle, Washington
98105-0371, USA. rebecca.johnson@seattlechildrens.org

Most adolescents and young adults (AYAs) with cancer will survive their disease,
and fertility issues are a major concern for this population. The ASCO and new
NCCN Clinical Practice Guidelines in Oncology for Adolescent and Young Adult
Oncology recommend that oncologists offer the option of fertility preservation to
all postpubertal AYAs before the start of potentially gonadotoxic chemotherapy or
radiotherapy, providing that the patient does not require emergent start of
therapy. Despite the published practice guidelines, many AYAs diagnosed with
cancer are still not offered fertility preservation, with oncologists citing lack
of time, lack of knowledge, and discomfort in discussing fertility and sexuality
with AYAs as reasons. Developing a systematic and coordinated multidisciplinary
strategy for fertility preservation referrals within a practice site may
streamline the referral process, off-loading some tasks from the oncologist and
potentially increasing patient satisfaction, provider satisfaction, and
compliance with the guidelines.

PMID: 23307983  [PubMed – in process]

39. Taiwan J Obstet Gynecol. 2012 Dec;51(4):495-505. doi: 10.1016/j.tjog.2012.09.003.

Hormone therapy for younger patients with endometrial cancer.

Lee WL, Lee FK, Su WH, Tsui KH, Kuo CD, Hsieh SL, Wang PH.

Department of Medicine, Cheng-Hsin General Hospital, Taipei, Taiwan.

The relationship between hormones and endometrial cancer is well known because
disease states, such as chronic anovulation and endogenous estrogen production
from hormone-secreting tumors (for example, granulosa cell tumor of the ovary),
are related to excess estrogen, and unopposed estrogen use might lead to
endometrial overgrowth, hyperplasia, and subsequent development of endometrial
carcinoma. Therefore, the possibility of using antihormone therapy in endometrial
carcinoma and/or its precancer lesions, such as simple hyperplasia with and
without atypia and complex hyperplasia with and without atypia, is always
supposed, as in the management of breast cancer. In addition, if women in whom
endometrial cancer is diagnosed are very young, some critical issues should be
considered, including the possibility of ovary preservation-partial preservation
of fertility and the possibility of both ovary and uterus preservation-complete
preservation of fertility. Other factors are also important to consider and
include oncologic risk, appropriateness of candidates for treatment, type of
hormone use, response rate of hormonal therapy, appropriate surveillance, and
additional counseling for issues such as anxiety about relapse and metastasis,
distress about side effects, advice of the family, advice of the medical staff,
and economic burden. This review will be focused on updated information and
recent knowledge of the use of hormones in the management of younger women with
endometrial cancer who want fertility preservation.

Copyright © 2012. Published by Elsevier B.V.

PMID: 23276551  [PubMed – in process]

40. Fertil Steril. 2012 Dec 21. pii: S0015-0282(12)02454-5. doi:
10.1016/j.fertnstert.2012.11.042. [Epub ahead of print]

Optimizing human oocyte cryopreservation for fertility preservation patients:
should we mature then freeze or freeze then mature?

Lee JA, Barritt J, Moschini RM, Slifkin RE, Copperman AB.

Reproductive Medicine Associates of New York, Mount Sinai School of Medicine, New
York, New York. Electronic address: jlee@rmany.com.

OBJECTIVE: To evaluate the maturation and post-thaw survival rates of immature
oocytes to determine whether in vitro maturation (IVM) should be attempted prior
to or after cryopreservation. DESIGN: Nonrandomized observational study. SETTING:
Private academic and clinical reproductive center. PATIENT(S): Patients (n = 71)
who donated immature unusable oocytes after vaginal oocyte retrieval (VOR) after
undergoing controlled ovarian hyperstimulation using a standard GnRH antagonist
protocol. INTERVENTION(S): Germinal vesicle (GV), metaphase I (MI), and metaphase
II (MII) oocytes (n = 175) were obtained from consenting IVF patients for fresh
IVM, post-thaw IVM, or control group. In the fresh IVM group, GV- and MI- stage
oocytes (n = 69) were cultured for 24 hours, matured in vitro (IVM-MII),
cryopreserved, thawed, and evaluated for survival. In the post-thaw IVM group,
GV- and MI- stage oocytes (n = 27) were frozen on day 0, thawed, evaluated for
survival, and cultured for 24-hour IVM. MII donor oocytes (n = 79) were
cryopreserved and thawed as a control. MAIN OUTCOME MEASURE(S): Survival
postfreeze and oocyte development to the MII stage was analyzed using a χ(2)
analysis. RESULT(S): Fresh IVM had a significantly higher maturation rate than
post-thaw IVM. CONCLUSION(S): Oocyte cryopreservation is important for patients
at risk of ovarian cancer, elective fertility preservation, and, potentially, for
ovum donation. The superior maturation rate of GV and MI oocytes in the fresh
versus post-thaw groups provides strong evidence for maturing oocytes to the MII
stage before cryopreservation.

Copyright © 2013 American Society for Reproductive Medicine. Published by
Elsevier Inc. All rights reserved.

PMID: 23266213  [PubMed – as supplied by publisher]

41. Lupus. 2013 Jan;22(1):81-6. doi: 10.1177/0961203312468624.

The impact of cyclophosphamide on menstruation and pregnancy in women with
rheumatologic disease.

Harward LE, Mitchell K, Pieper C, Copland S, Criscione-Schreiber LG, Clowse ME.

Department of Medicine, Medical University of South Carolina, USA.

BACKGROUND: While cyclophosphamide (CYC) can save the life of a young woman with
severe rheumatologic disease, it may lead to the long-term side-effects of
infertility and premature menopause. We compared the reproductive health
histories of young women with rheumatologic disease with and without prior CYC
exposure to identify the impact of this medication on this important component of
health.
METHODS: This research includes a case-series study of women diagnosed with SLE,
vasculitis, and scleroderma prior to age 35. Each patient completed a
questionnaire about desired childbearing, menstrual regularity, infertility, and
pregnancy history. Women with prior CYC therapy were queried about the use of
gonadotropin-releasing hormone agonists (GnRH-a) for fertility preservation. The
responses to this questionnaire were compared for women with and without CYC
exposure.
RESULTS: Of the 43 participants, 23 had prior CYC exposure and 20 were CYC naïve.
The current age of these groups was similar (average age 32), but women with
prior CYC were four years younger at diagnosis than women without CYC. More women
with prior CYC had cessation of menses in the year prior to the study (30.4% vs
0%, p < 0.05). Of the women with prior CYC exposure, those with loss of menses
were older at study enrollment, older at CYC treatment, and had a higher
cumulative CYC dose than those with preserved menstruation. While more women with
GnRH-a co-therapy during CYC had maintained menses, this difference did not reach
statistical significance. Women with prior CYC without GnRH-a co-therapy had a
higher frequency of nulliparity and had greater trouble conceiving than women
with GnRH-a co-therapy. Few pregnancies were conceived following CYC exposure and
all resulted in elective termination, miscarriage, or preterm birth.
CONCLUSION: In this cohort of young women with rheumatologic disease, more women
with prior CYC than without had amenorrhea, nulliparity, and infertility. GnRH-a
co-therapy may prevent these adverse effects of CYC.

PMID: 23263867  [PubMed – in process]

42. J Urol. 2013 Feb;189(2):647-50. doi: 10.1016/j.juro.2012.09.043. Epub 2012 Dec
20.

Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis
in men undergoing testosterone replacement therapy.

Hsieh TC, Pastuszak AW, Hwang K, Lipshultz LI.

Division of Urology, University of California-San Diego, San Diego, California,
USA.

PURPOSE: Testosterone replacement therapy results in decreased serum
gonadotropins and intratesticular testosterone, and impairs spermatogenesis,
leading to azoospermia in 40% of patients. However, intratesticular testosterone
can be maintained during testosterone replacement therapy with co-administration
of low dose human chorionic gonadotropin, which may support continued
spermatogenesis in patients on testosterone replacement therapy.
MATERIALS AND METHODS: We retrospectively reviewed the records of hypogonadal men
treated with testosterone replacement therapy and concomitant low dose human
chorionic gonadotropin. Testosterone replacement consisted of daily topical gel
or weekly intramuscular injection with intramuscular human chorionic gonadotropin
(500 IU) every other day. Serum and free testosterone, estradiol, semen
parameters and pregnancy rates were evaluated before and during therapy.
RESULTS: A total of 26 men with a mean age of 35.9 years were included in the
study. Mean followup was 6.2 months. Of the men 19 were treated with injectable
testosterone and 7 were treated with transdermal gel. Mean serum hormone levels
before vs during treatment were testosterone 207.2 vs 1,055.5 ng/dl (p <0.0001),
free testosterone 8.1 vs 20.4 pg/ml (p = 0.02) and estradiol 2.2 vs 3.7 pg/ml (p
= 0.11). Pretreatment semen parameters were volume 2.9 ml, density 35.2 million
per ml, motility 49.0% and forward progression 2.3. No differences in semen
parameters were observed during greater than 1 year of followup. No impact on
semen parameters was observed as a function of testosterone formulation. No
patient became azoospermic during concomitant testosterone replacement and human
chorionic gonadotropin therapy. Nine of 26 men contributed to pregnancy with the
partner during followup.
CONCLUSIONS: Low dose human chorionic gonadotropin appears to maintain semen
parameters in hypogonadal men on testosterone replacement therapy. Concurrent
testosterone replacement and human chorionic gonadotropin use may preserve
fertility in hypogonadal males who desire fertility preservation while on
testosterone replacement therapy.

Copyright © 2013 American Urological Association Education and Research, Inc.
Published by Elsevier Inc. All rights reserved.

PMID: 23260550  [PubMed – in process]

43. J Assist Reprod Genet. 2013 Jan;30(1):3-9. doi: 10.1007/s10815-012-9909-5. Epub
2012 Dec 15.

Evaluation of ovarian and testicular tissue cryopreservation in children
undergoing gonadotoxic therapies.

Babayev SN, Arslan E, Kogan S, Moy F, Oktay K.

Department of Obstetrics and Gynecology, New York Medical College, Valhalla, NY,
USA.

OBJECTIVE: Ovarian and testicular tissue cryopreservation are the only fertility
preservation options for sexually immature individuals. Because of their
experimental nature, it is important to determine safety and possible bundling
with other medicallyindicated procedures.
STUDY DESIGN: Prospective observational.
RESULTS: Cryopreservation indications included cancer in 75 % of females and 50 %
of males, while non-cancer indications included various hematological conditions.
Similar numbers of females (12/28) and males (3/9) underwent prior chemotherapy.
Females underwent laparoscopic (27/28) or robotic (1/28) approaches while
incisional biopsy was used in males. Bundling of ovarian and testicular
harvesting with other medicallyindicated procedures was performed in 42 % and 22
%, respectively. The operative time inclusive of bundled procedures was similar
(1.6 ± 0.1 vs. 0.9 ± 0.3 h) but the discharge time was significantly longer for
females than males (10.4 ± 0.6 vs. 4.6 ± 0.6 h, p<0.05) due to frequent bundling
of medically-indicated procedures in females. All procedures were successfully
completed without complications or significant blood loss.
CONCLUSIONS: Pediatric gonadal tissue cryopreservation can be combined with other
medically-indicated procedures to minimize the potential inconvenience,
additional anesthetic risks, and costs.

PMCID: PMC3553347 [Available on 2014/1/1] PMID: 23242649  [PubMed – in process]

44. Minerva Ginecol. 2012 Dec;64(6):461-75.

Fertility preservation in the male: from childhood to adulthood.

Masson P, Gerber JA, Brannigan RE.

Northwestern University Feinberg, School of Medicine, Chicago, IL, USA -
rebrannigan@gmail.com.

Approximately 50% of males will develop cancer during their lifetime. In the
past, oncologic therapies have largely been focused primarily on cure of the
underlying malignancy. With improvements in both diagnostic modalities and
treatments, pediatric and adult cancer patients are routinely surviving their
disease. For this large group of patients, survivorship issues have become a
major concern. Central among these survivorship issues is fertility. For males
diagnosed with a malignancy, impaired reproductive potential is often noted even
before any cancer therapy has been initiated. Furthermore, cancer treatments, in
the form of chemotherapy, radiation therapy, and surgery, can all have
potentially deleterious and lasting effects on male reproductive capability. For
these reasons, a change in oncologic treatment paradigms has occurred. Now, the
offer of fertility preservation to males diagnosed with cancer is a key component
of comprehensive oncologic care.

PMID: 23232531  [PubMed – in process]

45. Future Oncol. 2012 Dec;8(12):1567-73. doi: 10.2217/fon.12.144.

New trends in female fertility preservation: in vitro maturation of oocytes.

Berwanger AL, Finet A, El Hachem H, le Parco S, Hesters L, Grynberg M.

AP-HP, Service de Gynécologie-Obstétrique & Médecine de la Reproduction, Hôpital
Antoine Béclère, Clamart, F-92141, France.

As antineoplastic treatments have become more successful, an increasing number of
women with cancer survive to endure the long-term consequences of chemotherapy.
One of the most important of these consequences in young females is premature
ovarian failure and infertility. Owing to increasing survival rates, many of
these young women are seeking methods to preserve their fertility. Currently,
embryo/oocyte cryopreservation obtained after controlled ovarian stimulation
appears to provide the best fertility preservation option. However, patients may
not have enough time to undergo ovarian stimulation prior to chemotherapy and/or
have contraindications to exogenous gonadotropin administration owing to
estrogen-dependant tumors. In vitro maturation of oocytes is an attractive
alternative for fertility preservation in cancer patients because it does not
require ovarian stimulation and it can be performed at any time of the menstrual
cycle. In addition, this technique can be combined with ovarian tissue
cryobanking. In this review, we discuss the position of in vitro maturation of
oocytes in the fertility preservation strategy in young women.

PMID: 23231518  [PubMed – in process]

46. J Cancer Surviv. 2013 Mar;7(1):140-5. doi: 10.1007/s11764-012-0255-5. Epub 2012
Dec 11.

Pathways toward the future: points to consider for oncofertility oversight.

Rodriguez SB, Campo-Engelstein L, Clayman ML, Knapp C, Quinn G, Zoloth L, Emanuel
L.

Medical Humanities + Bioethics Program, Feinberg School of Medicine, Northwestern
University, Chicago, IL, USA, srodriguez@northwestern.edu.

INTRODUCTION: In September 2007, Northwestern University's Feinberg School of
Medicine received a $21.1 million dollar, 5-year grant from the National
Institutes of Health to fund the Oncofertility Consortium (OFC). Over the course
of the grant, those engaged with the psychological, legal, social, and ethical
issues arising from oncofertility provided recommendations to the OFC. The
inclusion of serious, real-time consideration of ethical issues as a funded focus
of the grant and the work of scholars in law, bioethics, and economics was a key
part of the process of research. Now that this grant has ended, this commentary
points to some of the issues that came forward during the 5 years of this
project. Because of the emerging status of oncofertility, these issues are ones
that need continued discussion and clarification, prompting our call for an
oversight mechanism to provide guidance for how this technology should proceed.
METHODS: An initial draft of this commentary arose from notes taken during a
small colloquium held to discuss the oversight of oncofertility following the
conclusion of the grant. This colloquium occurred in the fall of 2011. Using
these notes as a starting point, the draft was then sent to other researchers who
had been involved with the OFC in considering the psychological, legal, social,
and ethical issues related to fertility preservation for cancer patients during
the course of the grant. Finally, this commentary was further framed by the
authors' review of existing published and gray literature regarding issues
concerning fertility preservation for cancer patients.
RESULTS: We provide several points to consider and then offer two suggestions for
an oversight mechanism for research as it continues. DISCUSSION/CONCLUSIONS : We
assert the need not just for guidelines for the clinical practice of
oncofertility, but also for oversight of the scope of this emerging technology
because of its profound implications. We recognize that many long to a have a
child and form a family and that, for some, cancer interrupts this path. With the
conclusion of this grant, we call for the creation of a permanent oversight
mechanism to thoughtfully and earnestly consider how to guide oncofertility to
allow this emerging technology to be carefully considered as it develops.
IMPLICATIONS FOR CANCER SURVIVORS: The circumstances in which fertility
preservation should be discussed and the patients for whom fertility preservation
would be most suitable are important guideline issues for people who survive
cancer and for their treatment team. Oversight of the field of oncofertility
would strengthen the rights of cancer patients and help protect them from abuses
as well as alert health care professionals to their correlative duties to these
vulnerable patients and families.

PMCID: PMC3568233 [Available on 2014/3/1] PMID: 23229088  [PubMed – in process]

47. Arch Gynecol Obstet. 2012 Dec 7. [Epub ahead of print]

Effect of a gonadotropin-releasing hormone analogue on cyclophosphamide-induced
ovarian toxicity in adult mice.

Kishk EA, Mohammed Ali MH.

Department of Obstetrics and Gynecology, Faculty of Medicine, Suez Canal
University, Ismailia, Egypt, tete5500@yahoo.com.

PURPOSE: To evaluate the possible protective effect of low and high dose of
triptorelin, a GnRH analogue, on cyclophosphamide-induced ovarian toxicity in
adult female mice. METHODS: Thirty-six sexually mature, virgin, female mice were
divided randomly into six groups of six each: control group, low-dose triptorelin
(TL) group, high-dose triptorelin (TH) group, cyclophosphamide (CPA) group,
low-dose triptorelin plus cyclophosphamide (TL + CPA) group and high-dose
triptorelin plus cyclophosphamide (T + CPA) group. Mice in both the TL + CPA and
the TH + CPA groups were injected with 3.8 and 38 mg/kg of triptorelin
subcutaneously, respectively. Four weeks later, mice in the CPA, TL + CPA and
TH + CPA groups were injected with cyclophosphamide, intraperitoneally, at a dose
of 50 mg/kg. Ovaries were removed 4 weeks later and processed for light
microscopic examinations. RESULTS: Obvious destruction of ovarian structure and
significant depletion of primordial, primary, secondary and antral follicles were
demonstrated in the CPA group and compared with the control group, the difference
was statistically highly significant (p < 0.001), affirming the ovarian toxicity
of cyclophosphamide. In the TL + CPA group, there was a significant increase in
primordial, primary, secondary and antral follicles compared with the CPA group
(p < 0.05), showing the effect of triptorelin on ovarian protection. Regarding,
the high-dose GnRH agonist the difference was statistically highly significant
for primordial and primary follicles (p < 0.001). CONCLUSIONS: This study has
showed a dose-dependent protective effect of GnRH analogue on ovarian reserve
against ovarian toxic chemotherapy, thus demonstrating an important role of GnRH
analogues in fertility preservation.

PMID: 23224696  [PubMed – as supplied by publisher]

48. Breast Cancer Res Treat. 2013 Jan;137(2):571-7. doi: 10.1007/s10549-012-2361-5.
Epub 2012 Dec 9.

Impact of breast cancer on anti-mullerian hormone levels in young women.

Su HI, Flatt SW, Natarajan L, DeMichele A, Steiner AZ.

Division of Reproductive Endocrinology and Infertility and Moores UCSD Cancer
Center, University of California San Diego, 3855 Health Sciences Drive #0901, La
Jolla, CA 92093-0901, USA. hisu@ucsd.edu

Young women with breast cancer face treatments that impair ovarian function, but
it is not known if malignancy itself impacts ovarian reserve. As more breast
cancer patients consider future fertility, it is important to determine if
ovarian reserve is impacted by cancer, prior to any therapeutic intervention. A
cross-sectional study was conducted comparing if ovarian reserve, as measured by
anti-mullerian hormone (AMH), follicle stimulating hormone (FSH), and inhibin B
(inhB), differed between 108 women with newly diagnosed breast cancer and 99
healthy women without breast cancer. Breast cancer participants were ages 28-44
and were recruited from two clinical breast programs. Healthy women ages 30-44
without a history of infertility were recruited from gynecology clinics and the
community. The median age (interquartile range) was 40.2(5.5) years for breast
cancer participants and 33.0(4.6) years for healthy controls. The unadjusted
geometric mean AMH levels (SD) for breast cancer participants and controls were
0.66(3.6) and 1.1(2.9) ng/mL, respectively. Adjusting for age, body mass index,
gravidity, race, menstrual pattern, and smoking, mean AMH levels were not
significantly different between breast cancer participants and healthy controls
(0.85 vs. 0.76 ng/mL, p = 0.60). FSH and inhB levels did not differ by breast
cancer status. In exploratory analysis, the association between AMH and breast
cancer status differed by age (p-interaction = 0.02). AMH may be lower with
breast cancer status in women older than 37. In younger women, AMH levels did not
differ significantly by breast cancer status. Among the youngest of breast cancer
patients, ovarian reserve as measured by AMH, FSH, and inhibin B did not differ
significantly from healthy women of similar age. In older breast cancer patients,
ovarian reserve may be adversely impacted by cancer status. These findings
support the potential success and need for fertility preservation strategies
prior to institution of cancer treatment.

PMCID: PMC3540167 [Available on 2014/1/1] PMID: 23224236  [PubMed – in process]

49. Health Care Women Int. 2013;34(1):50-67. doi: 10.1080/07399332.2012.735729.

Fertility management after breast cancer diagnosis: a qualitative investigation
of women's experiences of and recommendations for professional care.

Kirkman M, Stern C, Neil S, Winship I, Mann GB, Shanahan K, Missen D, Shepherd H,
Fisher JR.

The Jean Hailes Research Unit, School of Public Health and Preventive Medicine,
Monash University, Melbourne, Victoria, Australia. Maggie.Kirkman@monash.edu

Breast cancer and its treatment in reproductive-age women can reduce fertility
and compromise family formation. To learn about women's experiences of
fertility-related cancer care we interviewed 10 women (aged 26-45), at least one
year postdiagnosis. Thematic analysis revealed that all women, including one who
chose to be child-free, valued fertility and motherhood. They reported
experiencing varied fertility-related care, from support for fertility
preservation to apparent disregard of their fertility concerns. Women's needs
were heterogeneous, but all wanted health care providers to communicate fertility
options and avoid assumptions about women's fertility desires while working to
extend each woman's life.

PMID: 23216096  [PubMed – indexed for MEDLINE]

50. Mol Hum Reprod. 2012 Dec 5. [Epub ahead of print]

The effects of whole ovarian perfusion and cryopreservation on endothelial
cell-related gene expression in the ovarian medulla and pedicle.

Onions VJ, Webb R, Pincott-Allen C, Picton HM, Campbell BK.

Division of Obstetrics and Gynaecology, School of Clinical Sciences, University
of Nottingham, Nottingham NG7 2UH, UK.

Fertility preservation by whole ovarian cryopreservation requires successful
cryopreservation of both the ovary and its vascular supply. Previous work has
indicated detrimental effects of both perfusion and cryopreservation on the
ovarian vasculature. This study assessed the effects of blood perfusion, alone or
in combination with cryopreservation, on functional effects in the follicle
population and ovarian function in vivo following short-term autotransplantation
of the tissue after vascular reanastomosis and measured acute changes in
endothelial cell-related gene expression within the ovarian medulla and pedicle.
Following autotransplantation for 7 days, primordial, transitional and primary
follicle densities were significantly reduced (P < 0.05) and stromal Ki67 and
caspase-3 expression significantly increased (P < 0.05) in cryopreserved but not
fresh or perfused whole ovaries. There was evidence of clot formation and
fluorescent microsphere (FMS) extravasation in the medulla of all cryopreserved
ovaries, indicating vascular damage. Utilizing a customized RT-PCR array or
conventional RT-PCR, we found that perfusion alone resulted in down-regulation in
the expression of caspase 6 and thrombospondin 1 (THBS1) genes in the medulla.
Following additional cryopreservation, endothelial nitric oxide synthase (eNOS),
endothelin 1, endothelin receptor A and Bcl-2 expression were significantly (P <
0.05) down-regulated. In the pedicle, both perfusion and cryopreservation caused
a (P < 0.05) down-regulation of eNOS and THBS1, and an up-regulation in Bax
expression. Perfusion also caused a down-regulation of TNF and up-regulation of
endothelin-2 expression (P < 0.05). In conclusion, this study has identified a
number of endothelial cell-related genes expressed in the medulla which are
acutely affected by both cryopreservation and perfusion, supporting the
hypothesis that both interventions have deleterious effects on endothelial cell
function.

PMID: 23204433  [PubMed – as supplied by publisher]

51. Stem Cells Transl Med. 2012 Sep;1(9):668-72. doi: 10.5966/sctm.2012-0076. Epub
2012 Sep 7.

Concise review: fertility preservation: an update.

González C, Boada M, Devesa M, Veiga A.

Department of Obstetrics, Gynecology and Reproduction, Institut Universitari
Dexeus, Barcelona, Spain.

Fertility preservation is an emerging field in medicine that enables men, women,
and children to maintain reproductive health when it is threatened by gonadotoxic
treatment. Patients affected by other nononcologic malignancies that can impair
spermatogenesis and ovogenesis can also benefit from fertility preservation
treatments. Age-related infertility can also be overcome by cryopreserving
gametes or embryos. The only established methods for fertility preservation in
male patients are sperm cryopreservation in postpubertal age and experimental
testicular tissue cryopreservation in prepubertal age. In adult women, oocyte
cryopreservation is the preferred option, whereas ovarian tissue cryopreservation
is the only possibility for prepubertal girls. Fertility preservation treatments
must be addressed through a multidisciplinary approach that involves
gynecologists, urologists, oncologists, pediatricians, and professionals in the
field of medically assisted reproduction to work in coordination to provide
patients with counseling and comprehensive information about fertility issues.

PMID: 23197873  [PubMed – indexed for MEDLINE]

52. J Bioeth Inq. 2012 Sep;9(3):311-6. doi: 10.1007/s11673-012-9378-7. Epub 2012 Jul
24.

The ethics of fertility preservation in transgender body modifications.

Murphy TF.

Department of Medical Education m/c 591, University of Illinois College of
Medicine at Chicago, Chicago, IL 60612-7309, USA. tmurphy@uic.edu

In some areas of clinical medicine, discussions about fertility preservation are
routine, such as in the treatment of children and adolescents facing cancer
treatments that will destroy their ability to produce gametes of their own.
Certain professional organizations now offer guidelines for people who wish to
modify their bodies and appearance in regard to sex traits, and these guidelines
extend to recommendations about fertility preservation. Since the removal of
testicles or ovaries will destroy the ability to have genetically related
children later on, it is imperative to counsel transgender people seeking body
modifications about fertility preservation options. Fertility preservation with
transgender people will, however, lead to unconventional outcomes. If transgender
men and women use their ova and sperm, respectively, to have children, they will
function as a mother or father in a gametic sense but will function in socially
reversed parental identities. There is nothing, however, about fertility
preservation with transgender men and women that is objectionable in its motives,
practices, or outcomes that would justify closing off these options. In any case,
novel reproductive technologies may extend this kind of role reversal in
principle to all people, if sperm and ova can be derived from all human beings
regardless of sex, as has happened with certain laboratory animals.

PMID: 23180331  [PubMed – in process]

53. Reprod Biol Endocrinol. 2012 Nov 24;10:98. doi: 10.1186/1477-7827-10-98.

FSH prevents depletion of the resting follicle pool by promoting follicular
number and morphology in fresh and cryopreserved primate ovarian tissues
following xenografting.

von Schönfeldt V, Chandolia R, Ochsenkühn R, Nieschlag E, Kiesel L, Sonntag B.

Department of Gynecology and Obstetrics, University of Münster, Münster, Germany.
barbara.sonntag@amedes-group.com.

ABSTRACT:BACKGROUND: Cryopreservation and transplantation of ovarian tissue is
one option for re-establishing ovarian function, but optimal conditions for graft
sustainment and follicular survival are still considered experimental. The
present study aims to analyze the effect of FSH treatment on the resting follicle
pool in fresh and cryopreserved primate ovarian tissues following xenografting.
METHODS: Ovarian tissues from adult marmosets were grafted freshly or following
cryopreservation to ovarectomized nude mice treated with FSH 25 IU twice daily
post transplantation or left untreated as controls. Grafts were retrieved 2 or 4
weeks after transplantation to evaluate the number and morphological appearance
of follicles.
RESULTS: Early start of FSH treatment within 1 week following transplantation
partly prevents primordial follicle loss in fresh and frozen-thawed tissues,
whereas after a 3 weeks time interval this effect is present only in fresh
tissues. A similar positive effect of early, but not later FSH treatment on
primary follicles is seen in fresh tissues compared to only marginal effects in
frozen-thawed tissues. The percentage of morphologically normal follicles is
generally increased in FSH treated tissues, whereas the percentage of primary
follicles over all primordial and primary follicles is increased by FSH only in
freshly-grafted tissues.
CONCLUSIONS: FSH treatment alleviates depletion of the resting follicle pool and
promotes normal follicular morphology both in freshly and frozen-thawed grafted
tissues. In previously cryopreserved tissues, applying to most of the tissues
intended for clinical use in fertility preservation attempts, its positive effect
on primordial follicle numbers and potential graft sustainment is dependent on an
early start of treatment within one week of transplantation.

PMCID: PMC3560100
PMID: 23176179  [PubMed – in process]

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