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Objective: To study how genetics may play a role in determining risk of chemotherapy-related amenorrhea (CRA) in young women with breast cancer., Design: Genome-wide association study., Setting: Not applicable., Patient(s): Premenopausal women ≤45 years of age enrolled in one of these three trials were included if they had at least one menstrual case report form after chemotherapy ended and if they were of European ancestry. Forms during and up to 3 months after receipt of GnRH agonist were excluded., Intervention(s): None., Main Outcome Measure(s): The association of single-nucleotide polymorphisms with post-chemotherapy menstruation adjusted for trial and arm, age, tamoxifen use, and nodal status., Result(s): The median age of the 1,168 women was 41 years (range 19-45). Among these, 457 (39%) never resumed menses after chemotherapy. Older age, tamoxifen use, and node-negative disease were associated with increased risk of CRA. Adjusting for these, rs147451859, in an intron of PPCDC (phosphopantothenoylcysteine decarboxylase), and rs17587029, located 5' upstream of RPS20P11 (ribosomal protein S20 pseudogene 11), were associated with post-chemotherapy menstruation., Conclusion(s): Genetic variation may contribute to risk of CRA. Better prediction of who will experience CRA may inform reproductive and treatment decision making in young women with cancer., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To systematically review the reporting of MII (MII) oocyte development after xenotransplantation of human ovarian tissue., Design: Systematic review in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)., Setting: Not applicable., Patient(s): Not applicable., Intervention(s): Formation of MII oocytes after xenotransplantation of human ovarian tissue., Main Outcome Measure(s): Any outcome reported in Pubmed., Result(s): Six publications were identified that report on formation of MII oocytes after xenotransplantation of human ovarian tissue., Conclusion(s): Xenografting of human ovarian tissue has proved to be a useful model for examining ovarian function and follicle development in vivo. With human follicles that have matured through xenografting, the possibility of cancer transmission and relapse can also be eliminated, because cancer cells are not able to penetrate the zona pellucida. The reported studies have demonstrated that xenografted ovarian tissue from a range of species, including humans, can produce antral follicles that contain mature (MII) oocytes, and it has been shown that mice oocytes have the potential to give rise to live young. Although some ethical questions remain unresolved, xenotransplantation may be a promising method for restoring fertility. This review furthermore describes the value of xenotransplantation as a tool in reproductive biology and discusses the ethical and potential safety issues regarding ovarian tissue xenotransplantation as a means of recovering fertility., (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To report the results of 20 orthotopic retransplantations of cryopreserved ovarian tissue after cancer treatment., Design: Retrospective analysis., Setting: Tertiary gynecology department., Patient(s): Twenty patients with malignant disease: 11 with hematological malignancies (55%), four with breast cancer (20%), three with anal cancer (15%), and two with ovarian cancer (10%); the mean age before oncological treatment was 30.5 years., Intervention(s): Ovarian tissue was removed from patients in various centers in Germany in 2005-2009. All patients received chemotherapy and/or radiotherapy. Afterward, 17 patients had complete premature ovarian insufficiency, while three still showed some ovarian activity. Overnight transportation of tissue before freezing was necessary in eight cases. Cryopreservation followed slow freezing protocols in all cases. Retransplantation was performed at Erlangen University Hospital 3.75 years after extraction, on average. Thawed tissue was transplanted into a peritoneal pouch in the broad ligament region, below the tube, in 16 cases. Fragments were sutured both onto the remaining ovary and into a peritoneal pouch in four cases., Main Outcome Measure(s): Restoration of ovarian activity, pregnancy, birth., Result(s): Ovarian activity resumed in all patients except one. Seven patients conceived, with one miscarriage and four ongoing pregnancies. Four patients delivered healthy babies. One pregnancy and live birth after oocyte donation need to be considered separately., Conclusion(s): These data clearly demonstrate that preserving fertility by cryopreserving ovarian tissue is a successful and safe clinical option that can be considered for selected cancer patients., (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the capacity of human frozen-thawed ovarian follicles matured in xenografts to form metaphase II (MII) oocytes after xenotransplantation and exogenous stimulation., Design: Prospective controlled animal study., Setting: University hospital gynecology research unit., Patient(s): Ovarian fragments were obtained from 17 women with malignant diseases who wished to cryopreserve ovarian tissue for later pregnancy before chemotherapy., Animal(s): Eighty-eight female severe combined immunodeficient (SCID) mice., Intervention(s): Cryopreserved human ovarian tissue was grafted into oophorectomized SCID mice. The mice were divided into three groups: Group A received hMG alone every 2 days for a maximum of 24 weeks; group B additionally received nRH agonist (GnRHa) every 4 weeks; and group C was an untreated control group., Main Outcome Measure(s): Follicular density, morphology, proliferation, oocyte maturation, malignant cell contamination., Result(s): Follicle survival and development were similar in all three groups. No significant interactions between the stimulation protocols and grafting duration were noted. Three MII oocytes were observed in grafted follicles. Two MII oocytes were harvested without stimulation. None of the mice showed signs of reintroduced malignancy, nor did microscopic evaluation of the grafts raise any suspicion of residual malignant disease., Conclusion(s): After xenotransplantation, human primordial follicles can be matured to MII oocytes even without stimulation. Administering human gonadotropin and GnRHa does not enhance the developmental capacity of xenografted oocytes. The optimal stimulation schedule for grafted tissue remains unknown., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To study women with a poor response to ovarian hormone stimulation, known as low responders. Genetic defects in the FSH receptor gene (FSHR) were analyzed as well as antimüllerian hormone (AMH) for ovarian reserve., Design: Retrospective cohort study., Setting: University hospital., Patient(s): Two hundred fifty-nine patients total: 74 low responders; 88 patients receiving assisted reproduction therapy (ART) with a normal ovarian response; and 97 women with a normal fertility status., Intervention(s): DNA from patients was analyzed using real-time polymerase chain reaction. Serum concentrations of AMH were assessed using ELISA., Main Outcome Measure(s): The FSHR variants Asn680Ser (rs6166), Ala189Val (rs121909658), Ile160Thr (rs121909659), Thr449Ile (rs28928870) and the serum AMH concentrations were assessed., Result(s): With the exception of the frequent Asn680Ser polymorphism, no homozygotic SNPs of FSHR were found. In the group of ART patients, Thr160/Ile160 variants were more frequent in comparison with women with normal fertility. The Ser680/Ser680 was more frequent in ART patients than in women with normal reproductive function. The rate of live births was markedly reduced, particularly in the low responder group. No difference was noted in the distribution of the Ala189Val and Thr449Ile variant. Low serum AMH values were observed in 75% of the low responder group., Conclusion(s): FSHR gene variations such as Asn680Ser, Ala189Val, Thr449Ile, and Ile160Thr did not seem to be a decisive factor of poor response to fertility treatment, whereas the low ovarian reserve determined by AMH is considered more crucial., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the first live birth after transplantation of ovarian tissue following overnight transportation of the tissue before freezing., Design: Technical note., Setting: University department of obstetrics and gynecology., Patient(s): A 25-year-old cancer survivor with previous Hodgkin disease and relapse., Intervention(s): The ovarian tissue was kept cool for >20 hours in a special transport medium and a special cooling device before it was cryopreserved. After premature ovarian failure due to preconditioning chemotherapy for bone marrow transplantation, the cryopreserved ovarian tissue was transplanted orthotopically., Main Outcome Measure(s): Resumption of ovarian function after transplantation, recovery of fertility, and pregnancy., Result(s): Ovarian function returned in the patient 3 months after transplantation, as shown by follicle development and estrogen production. During the fifth menstrual cycle, mild stimulation with FSH was initiated in accordance with a low-dose protocol. When ultrasonography revealed a follicle 18-20 mm in size in the ovarian graft, hCG was added and the patient had sexual intercourse at the optimal time point. On day 14 of the luteal phase, hCG concentration and vaginal echography confirmed a viable intrauterine pregnancy, which resulted in a healthy live birth., Conclusion(s): Overnight transportation of ovarian tissue appears to be possible in combination with appropriate transportation logistics. However, further investigations are needed before this procedure can be offered as a chance for women to preserve fertility independently of direct access to a tissue-processing bank., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To compare different diagnostic procedures for staging malformations associated with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome., Design: Retrospective two-center cohort study (Canadian Task Force classification II-2)., Setting: University hospital., Patient(s): One hundred and thirty-eight women with MRKH., Intervention(s): Clinical examinations, abdominal or perineal/rectal ultrasound, magnetic resonance imaging (MRI), and laparoscopy., Main Outcome Measure(s): Agreement between the results obtained with the other methods and the results obtained with the reference methods for correct staging of malformations, presented as kappa values (κ)., Result(s): The VCUAM (vagina cervix uterus adnex-associated malformation) classification system was used to classify genital malformations in 138 women with MRKH. The reference methods for examining the individual organs were: vagina-clinical examination; cervix/uterus and adnexa-laparoscopy; and urinary tract malformations-MRI. The values obtained were as follows. Vagina was κ 0.74 for MRI versus clinical examination; ultrasound and laparoscopy did not allow adequate description of vaginal malformations. Cervical findings were rarely detailed with any of the imaging methods. Uterus was κ 0.93 for MRI versus laparoscopy, and κ 0.83 for ultrasound. For adnexa, only laparoscopy was able to describe the morphology adequately. The urinary tract was κ 0.87 for ultrasound versus MRI., Conclusion(s): For the correct staging of malformations associated with MRKH, MRI or a combination of clinical examination and ultrasound are equivalent. However, none of the imaging methods adequately describes adnexal morphology., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

This study examined the possible presence of malignant cells in ovarian cortex from patients with ovarian tumors after xenografting of the ovarian tissue into severe combined immunodeficiency mice. None of the mice presented symptoms of reintroduced malignancy nor did microscopic and immunohistochemical evaluation of the grafts raise any suspicion of residual malignant disease., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the impact of testosterone (T) administration to female-to-male transsexuals (FtMs) on insulin resistance and lipid parameters and to compare the effects with women with polycystic ovary syndrome (PCOS)., Design: Cohort analysis., Setting: University hospital., Patient(s): Twenty-nine FtMs and 240 women with PCOS., Intervention(s): Screening panel, ultrasound of the ovaries, hormone, lipid, and glucose and insulin measurements., Main Outcome Measure(s): Endocrine, metabolic parameters, and insulin resistance., Result(s): The PCOS women had significantly higher fasting, 1-h, and 2-h insulin levels and a significantly lower insulin sensitivity index compared with FtMs before and after their T treatment. There were higher triglyceride levels and lower high-density lipoprotein cholesterol levels upon T treatment in FtMs compared with the PCOS women. Women with PCOS had higher body mass index (BMI) values. Positive correlations between insulin resistance indices and BMI were found only in women with PCOS., Conclusion(s): Testosterone administration by itself showed little detrimental influence on insulin resistance indices, but it had significant effects on lipid profiles. Compared with T, BMI had a greater impact on insulin resistance in women with PCOS., (Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the impact of smoking on endocrine, metabolic, and clinical parameters in women with polycystic ovary syndrome (PCOS)., Design: Cohort analysis., Setting: University hospital., Patient(s): 346 women with PCOS, including 98 smokers and 248 nonsmokers., Intervention(s): Screening panel, including physical examination, weight and height measurement, and ultrasound examination of the ovaries, and hormone and insulin measurements., Main Outcome Measure(s): Clinical, metabolic, and endocrine parameters, oral glucose tolerance test, calculation of insulin resistance indexes., Result(s): In women with PCOS, smoking was associated with statistically significantly increased levels of fasting insulin and calculated free testosterone (cFT) and with a raised free androgen index (FAI) score, which resulted in aggravated scores on the homeostatic model for assessment of insulin resistance (HOMA-IR). However, no differences were observed between the smoking and nonsmoking groups with regard to the clinical parameters for hirsutism, acne, ovulatory function (classified as eumenorrhea, oligomenorrhea, and amenorrhea), or polycystic ovaries using the ultrasound criteria recommended according to the Rotterdam definition., Conclusion(s): In women with PCOS, smoking is associated with increased free testosterone and fasting insulin levels, resulting in aggravated insulin resistance. However, there were no differences between smokers and nonsmokers when clinical parameters were compared., (Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To compare high-sensitivity C-reactive protein (hs-CRP) with CRP as a soluble serum marker for the diagnosis of women with endometriosis., Design: Prospective nonrandomized controlled trial (Canadian Task Force classification II-1)., Setting: University hospital., Patient(s): Eighty-two women were laparoscopically evaluated. No endometriosis was diagnosed in 34 women (the non-E group). Endometriosis was confirmed by histology in 48 women (the E group). Eighty-two women did not undergo laparoscopic evaluation (the unknown-E group). Afterward, the women were staged according to the revised American Society for Reproductive Medicine criteria (r-ASRM)., Intervention(s): CRP and hs-CRP were measured initially before laparoscopy., Main Outcome Measure(s): The hs-CRP and CRP levels and the correlation of those parameters with the stage of the disease., Result(s): There was a trend toward higher CRP levels and higher hs-CRP levels in the E group, while the lowest levels of both markers were found in the non-E group. There was a significantly lower hs-CRP level in the non-E group in comparison with the CRP level in this group. No differences between the different stages of the disease were found with either marker., Conclusion(s): Measurement of the two markers did not appear to be advantageous for the diagnosis of endometriosis independent of the stage of the disease. Nevertheless, a very low hs-CRP level might serve as a marker for an absence of endometriosis., (Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the contractile response of the perfused swine uterus to various receptor pathways (oxytocin, prostaglandins, and muscarine)., Design: An extracorporeal perfusion model of the swine uterus was used that keeps the uterus in a functional condition and is appropriate for the study of physiologic questions., Intervention(s): Oxytocin-, prostaglandin-, and carbachol-induced uterine contractility and peristalsis were assessed using an intrauterine double-chip microcatheter., Setting: University hospital., Main Outcome Measure(s): Intrauterine pressure profiles., Result(s): A dose-dependent increase in intrauterine pressure (IUP) in the isthmus uteri and corpus uteri was observed after the administration of prostaglandin F(2alpha) (PGF(2alpha)) and oxytocin, which reached a plateau after further stimulation. A dose-dependent increase in IUP in the isthmus uteri and corpus uteri was also observed after the administration of prostaglandin E(1) (PGE(1)) and prostaglandin E(2) (PGE(2)), with a plateau in IUP in the middle-concentration range and a decrease during the further course of stimulation. After administration of PGE(1), PGE(2), and PGF(2alpha), different directions of contraction waves were also observed. Carbachol also showed a unique contractility pattern, with isolated, very powerful, dose-dependent contractions with an IUP gradient, suggesting directed transport from the upper region to the lower region., Conclusion(s): This study demonstrated that oxytocin, the prostaglandins, and carbachol modulate contractility in nonpregnant swine uteri in a characteristic way, resulting in different contractility patterns.

This is the first report showing a hormonal and histologic discrepancy in cryopreserved human ovarian tissue 11 months after orthotopic autotransplantation. The presence of antral follicles was observed although the hormonal values had returned to castrated levels.

This study evaluated in vivo whether the flare-up effect of GnRH agonists can be suppressed through pretreatment with a GnRH antagonist. The classic flare-up effect caused by 3.8 mg goserelin acetate could not be suppressed through pretreatment using a single dosage of 3.24 mg cetrorelix acetate.

This study evaluated the effect of gonadotropin stimulation on the primordial follicle reserve of cryopreserved human ovarian tissue after transplantation in severe combined immunodeficient mice. We found that prolonged gonadotropin stimulation significantly reduces primordial follicles.