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Background: Permanent sterilization is one of the most common methods of birth control in the United States and around the world. A small subset of women will regret their decision and desire future fertility. For these women, the options include in vitro fertilization (IVF) or surgical reversal. Surgical reversal, specifically via tubal reanastamosis, is an important choice to consider. Surgical reversal can be accomplished via three different general approaches including laparotomy, conventional laparoscopy, and robot-assisted approaches. Unfortunately, surgical reversal is becoming a lost art. Objective: To compare and contrast pregnancy success rates, ectopic pregnancy rates, and cost between the surgical methods and IVF. Methods: We conducted a literature review via Pubmed with keywords as listed below. Conclusion: Laparoscopic tubal reanastomosis is the best approach for women

Objective To determine whether follicle flushing during oocyte retrieval improves live birth or secondary outcomes in assisted reproductive technology (ART). Design Systematic review and meta-analysis. Setting Not applicable. Patient(s) Women undergoing ART using autologous gametes. Intervention(s) A systematic search of PubMed, EMBASE, Cochrane Database, and Web of Science for randomized controlled trials comparing follicle flushing to direct aspiration during oocyte retrieval published in English between 1989 to 2020. Main Outcome Measure(s) Live birth as primary outcome, and clinical and ongoing pregnancy, total and mature metaphase II (MII) oocytes retrieved, and operating time as secondary outcomes. Result(s) Eleven studies were included totaling 1,178 cases. No difference in live birth was demonstrated between follicle flushing and direct aspiration. Clinical pregnancy and ongoing pregnancy were not improved with flushing. Total oocyte and MII yield were lower with flushing compared with direct aspiration. Procedure time was increased with flushing by 2 minutes in poor responders and 9 minutes in normal responders. Other sensitivity analyses did not demonstrate any changes, except the difference in MII yield was no longer statistically significant. Conclusion(s) Follicle flushing during oocyte retrieval increases procedure time and does not improve live birth or secondary ART outcomes. Randomized data do not support the use of follicle flushing as an intervention in ART.

To compare clinical and ongoing pregnancy after natural cycle (NC) intrauterine insemination (IUI) versus ovarian stimulation (OS) IUI in ovulatory women undergoing therapeutic donor insemination (TDI).Retrospective cohort.Single infertility center.A total of 76,643 IUI cycles in patients treated with intrauterine insemination were examined. Women undergoing TDI in the absence of diagnosed female factor infertility were included.NC TDI or OS TDI with either clomiphene citrate or letrozole.Clinical and ongoing pregnancies were analyzed by generalized estimating equations adjusting for age, body mass index, total motile sperm at time of insemination and cycle number. Ongoing multiple gestations were examined as a secondary outcome.Six thousand one hundred ninety-two TDI cycles from 2,343 patients (711 patients without repeated IUI cycles) met inclusion criteria and were available for analysis (3,837 NC and 2,355 OS). There was no difference in mean age between the two groups (NC, 34.2 years vs. OS, 34.3 years). Probability of clinical and ongoing pregnancy was higher in the OS cohort compared with the NC cohort (OS, 22.4% vs. NC, 18.7% and OS, 15.4% vs. NC, 14.9%, respectively). However, OS significantly increased ongoing multiple gestations (OS, 10.8% vs. NC, 2.4%).Ovarian stimulation in TDI cycles resulted in a4% increase in clinical and1% increase in ongoing pregnancy, and more than fourfold increase in ongoing multiple gestations. Natural cycle IUI should be considered as a first-line treatment for ovulatory women who need donor insemination.

Lifestyle modification is widely considered to be the cornerstone of polycystic ovary syndrome (PCOS) treatment. However, 45% of women with PCOS have reported that they have never been provided information about lifestyle management. This highlights a significant gap in knowledge and is reflective of the lack of evidence-based guidance for lifestyle modification. While more detailed and comprehensive studies are being performed, it is necessary for health professionals to develop effective action plans utilizing the available evidence. This chapter aims to provide a comprehensive review of the current data regarding the impact of lifestyle modifications on the disease course of PCOS.

Anti-müllerian hormone (AMH) is an established marker of ovarian reserve that decreases with age. Though the pool of ovarian follicles is established during fetal development, impacts of in utero exposures on AMH are uncertain. Thus, we sought to evaluate associations of in utero exposures with AMH of adult daughters with a prospective cohort study of adult daughters at university medical centers. Women noted their mother’s reported use of diethylstilbestrol (DES), vitamins, tobacco, alcohol, and caffeine during pregnancy, and their mother’s occupation during pregnancy. All participants were reproductive age women (18–40 years) enrolled in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial. Serum AMH concentrations were measured at baseline prior to conception and categorized using clinical guidelines. Multinomial regression models estimated associations between each exposure and high (>3.5 ng/mL) and low (

Objective To describe fertility characteristics, outcomes of oocyte cryopreservation cycles, and safety of ovarian stimulation in patients with GATA binding protein 2 (GATA2) deficiency, dedicator of cytokinesis 8 (DOCK8) deficiency, and sickle cell disease (SCD) preparing for hematopoetic stem cell transplantation (HSCT). Design Retrospective case series. Setting The National Institutes of Health. Patient(s) Female patients with GATA2 deficiency, DOCK8 deficiency, and SCD aged between 13 and 38 years. Intervention(s) None. Main Outcome Measure(s) Demographic and ovarian reserve parameters, stimulation outcomes, and adverse event occurrences were collected through chart review. Descriptive statistics were used to identify trends within disease subcategories. Result(s) Twenty-one women with GATA2 deficiency, DOCK8 deficiency, and SCD underwent fertility preservation prior to HSCT. Patients with DOCK8 deficiency had the lowest mean age (16.5 years old) and antimullerian hormone (0.85 ng/mL). Patients with GATA2 deficiency had the highest antral follicle count and antimullerian hormone (25.77 and 5.07 ng/mL, respectively). Baseline follicle-stimulating hormone, luteinizing hormone, and estradiol were comparable between the cohorts. The duration of stimulation was similar (10.43 to 11.25 days) across all groups. Comparable peak estradiol levels were achieved across the cohorts. Patients with SCD had the highest mature (MII) oocyte yield (10.71). Three patients experienced complications related to stimulation: pain crisis in a patient with SCD, pulmonary embolism, and zero oocytes cryopreserved in a patient with GATA2 deficiency. Conclusion(s) This study offers insight into controlled ovarian stimulation in patients with these conditions prior to HSCT. Oocyte cryopreservation can be performed successfully, although adverse events must be considered. Following the outcomes of gamete use in this cohort will serve to further our knowledge of the true reproductive potential of this population.

The use of assisted reproduction among women in relationships with other women has increased in the United States over the past decade as a result of increased legal access and social acceptance. Despite this shift, limited studies currently exist to guide optimal fertility care for this growing patient population of women seeking assisted reproduction. In this Commentary, assisted reproduction will be meant to include ovulation induction, intrauterine insemination (IUI), and in vitro fertilization (IVF). Conflicting studies suggest that self-identified lesbian women may demonstrate an increased prevalence of polycystic ovarian syndrome. Most available studies find that a woman's sexual orientation does not affect the outcome of fertility treatment. Self-identified lesbian women undergoing donor sperm IUI and IVF have similar pregnancy and live-birth rates as heterosexual women. Better evidence regarding patient demographics and comorbidities, underlying etiologies of subfertility, and assisted reproductive outcomes among women building families with other women is needed to optimize care.

Polycystic ovarian syndrome (PCOS) is a common endocrinopathy with many clinical manifestations. The effects on women's lives start at puberty and can last throughout her lifetime. Women frequently experience anovulatory menstrual cycles, infertility, hirsutism, obesity and increased risk of diabetes mellitus, hypertension, lipid abnormalities, and metabolic syndrome. PCOS is a heterogenous disorder, and a diagnosis of exclusion. In general, women afflicted will have menstrual irregularities, ultrasound findings of abnormal ovarian size and morphology, and clinical or laboratory evidence of hyperandrogenism. This chapter reviews the current understanding of PCOS, associated metabolic abnormalities, and diagnosis in reproductive-aged women, as well as adolescents.

There are few treatments for patients with recurrent pregnancy loss (RPL) or recurrent implantation failure (RIF). Women with RPL and unexplained infertility have lower T regulatory cell (T(reg)) expression when compared to fertile controls. A murine model has been developed with depletion of regulatory T cells (DEREG) after administration of diphtheria toxin (DT), resulting in smaller litter sizes, secondary to embryo implantation failure. Numerous murine studies have shown that adoptive transfer of CD4(+)CD25(+)FoxP3(+) T(regs) from donors improves litter sizes in DEREG mice with depleted T(regs). Our hypothesis is that DEREG mice treated with a single dose of DT will deplete T(regs) and subsequently decrease litter sizes and that treatment with rapamycin (sirolimus; Pfizer) during the time of embryo implantation will increase T(regs) and restore litter sizes nearly back to normal levels. Syngeneic mating of DEREG mice after depletion of T(regs) resulted in smaller litter sizes and this defect was reversed when these DEREG mice were treated with rapamycin at the time of embryo implantation. The importance of T(regs) at the time of embryo implantation has been well established and immunotherapy treatments, such as rapamycin (mammalian target of rapamycin inhibitor), may prove to be an effective treatment for patients with RPL, RIF, or unexplained infertility with low T(reg).

A crisis is occurring in that reproductive endocrinologists are not doing the surgeries that are a part of their discipline. We list those procedures as a blueprint for training reproductive endocrinologists.

Research question Is ovulation suppression with progestins, requiring a freeze-all approach and subsequent frozen embryo transfer resulting from progestenic endometrial changes, cost-effective compared with gonadotropin releasing hormone analogues (GnRH) during assisted reproduction cycles. Design Cost-effectiveness analysis derived from a PubMed literature search of average US costs of GnRH agonist and antagonist IVF cycles. Results In all fresh IVF cycle models, progestin cycles were more expensive owing to the additional costs of increased gonadotropin use, embryo freezing and subsequent frozen embryo transfer (FET). The average cost per live birth with progestins ($32,466–$56,194) was higher than fresh IVF cycles with short (flare) GnRH agonist ($4,447–$12,797 higher) and GnRH antagonist ($1,542–$9,893 higher). When analyzing an initial embryo transfer plus additional FET in patients not initially pregnant, progestin cycles were still more expensive per live birth compared with conventional protocols. When planned freeze only cycles were analyzed, progestins became more cost-effective per live birth compared with antagonist cycles ($2,079 lower) but remained more expensive than short agonist cycles ($823 more expensive). Conclusions Ovulation inhibition in IVF using progestins requires a freeze-only approach of embryos, and thus progestin use was not cost-effective compared with fresh embryo transfer cycles. Progestins, however, may be cost-effective compared with GnRH antagonist in planned freeze only cycles such as in preimplantation genetic testing or fertility preservation.

To examine the relationship of preconception hemoglobin A1c, a marker of cumulative exposure to glucose over the preceding 2-3 months, with time to pregnancy, pregnancy loss, and live birth among fecund women without diagnosed diabetes or other medical diseases.A secondary analysis of a prospective cohort of women participating in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial.Four US academic medical centers.A total of 1,194 healthy women aged 18-40 years with a history of one or two pregnancy losses attempting spontaneous conception were observed for up to six cycles while attempting pregnancy and throughout pregnancy if they conceived.Not applicable.Time to pregnancy, human chorionic gonadotropin pregnancy, clinical pregnancy, pregnancy loss, and live birth.Although increasing preconception A1c level was associated with reduced fecundability (fecundability odds ratio [FOR] per unit increase in A1c 0.74; 95% confidence interval [CI] 0.57, 0.96) in unadjusted models and models adjusted for age, race, smoking and treatment arm (FOR 0.79; 95% CI 0.60, 1.04), results were attenuated after further adjustment for body mass index (FOR 0.91; 95% CI 0.68, 1.21). Preconception A1c levels among women without diagnosed diabetes were not associated with live birth or pregnancy loss.Among healthy women without diagnosed diabetes, we observed no association of A1c with live birth or pregnancy loss. The association between A1c and fecundability was influenced by body mass index, a strong risk factor for both diabetes and infertility. These data support current recommendations that preconception A1c screening should be reserved for patients with risk factors for diabetes.ClinicalTrials.gov: NCT00467363.

Steroid-producing cells contain key cytochrome P450 enzymes, such as side-chain cleavage (P450-SCC) and 17α-hydroxylase (17α-OH). They are required for steroid hormone synthesis and considered antigens associated with Addison's disease and autoimmune primary ovarian insufficiency (POI). We studied an animal model for human autoimmune POI in mice with autoimmune oophoritis induced by neonatal thymectomy performed at day 3 (TX3). We previously identified an oocyte-specific protein as a major antigen inciting autoimmune oophoritis in mice. In this study, we characterized ovarian steroid-producing cell antigens. Using indirect immunofluorescence staining, we tested immune reactions in mouse ovarian and adrenal tissue sections with sera from TX3 female mice. More than half of the TX3 mice (8 of 15) produced antibodies reacting with both ovarian and adrenal steroid-producing cells, including some that reacted to oocytes as well. We produced recombinant proteins for the three key steroidogenic enzymes 17α-OH, P450-SSC, and 3β-hydroxysteroid dehydrogenase (3β-HSD) and tested their immune reactions with individual mouse sera. By immunoblotting, all mouse sera that reacted with the steroid-producing cells (n = 8) were shown to react with the P450-SCC, but not with the 17α-OH or 3β-HSD recombinant proteins. The sham-operated mouse sera and TX3 mouse sera negative for steroid-producing cells did not react with the P450-SCC recombinant protein. Our findings indicate that the P450-SCC is a specific and unique major antigen within the ovarian steroid-producing cells. Given their similarity of predicted antigenicity, we assume that P450-SCC acts in human autoimmune POI as it does in mouse autoimmune oophoritis.

Objective To examine the outcomes of in vitro fertilization with intracytoplasmic sperm injection (IVF-ICSI) in couples in whom the male partner has a karyotypic abnormality or Y chromosome microdeletion (YCM). Design Retrospective cohort. Setting Single infertility center. Patient(s) Couples treated with IVF-ICSI from January 2014 to April 2019 with male factor infertility, sperm concentration of

Polycystic ovarian syndrome and its associated endocrine abnormalities comprise one of the most common metabolic spectrum disorders within the human race. Because of the variance in phenotypic expression among individuals and within family lineages, attention has been turned to genetic and epigenetic changes in which the root cause of the disorder may lie. Further understanding of DNA/histone methylation and microRNA patterns may help to improve the accuracy of diagnosis and lead to future treatment options.

Infertility affects 12 to 18% of couples in the United States and may be due to female factors, male factors, or both. A systematic evaluation of the common causes of infertility can identify conditions that may be treated by the obstetrician-gynecologist to help the couple achieve their family-building goals or those that require referral to a subspecialist. This review discusses current recommendations regarding the workup and treatment of the common causes of infertility, including tubal and pelvic factors, ovulatory disorders, and male factors. Advances in assisted reproductive technology are also discussed, including the use of genetic screening in in vitro fertilization and fertility preservation options for individuals facing gonadotoxic therapy. This review contains 6 figures, 8 tables, and 53 references. Key words: anovulation, assisted reproductive technology, clomiphene citrate, infertility, letrozole, oocyte cryopreservation, ovulation induction, semen analysis, tubal factor, uterine factor

Objective This study aimed to examine whether prenatal low-dose aspirin (LDA) therapy affects risk of cesarean versus vaginal delivery. Study design This study is a secondary analysis of the randomized clinical effects of aspirin in gestation and reproduction (EAGeR) trial. Women received 81-mg daily aspirin or placebo from preconception to 36 weeks of gestation. Mode of delivery and obstetric complications were abstracted from records. Log-binomial regression models estimated relative risk (RR) of cesarean versus vaginal delivery. Data were analyzed among the total preconception cohort, as well as restricted to women who had a live birth. Results Among 1,228 women, 597 had a live birth. In the intent-to-treat analysis, preconception-initiated LDA was not associated with risk of cesarean (RR = 1.02; 95% confidence interval [CI]: 0.98-1.07) compared with placebo. Findings were similar in just women with a live birth and when accounting prior cesarean delivery and parity. Conclusion Preconception-initiated daily LDA was not associated with mode of delivery among women with one to two prior losses. Key points · Aspirin was not associated with risk of cesarean section.. · Aspirin was not associated with mode of delivery.. · No increased risk of bleeding with use of aspirin..

Polycystic ovary syndrome is a common endocrinopathy that has been associated with many medical conditions across nearly every specialty. This chapter reviews the current understanding of polycystic ovary syndrome and associated medical conditions.

Melvin Taymor's daughter, Julie Taymor, directed the musical version of The Lion King, which won six Tony Awards. Known for her revolutionary staging, she became the first woman to be awarded a Tony for Best Direction of a Musical.

OBJECTIVE To characterize variation in circulating vascular endothelial growth factor (VEGF) and its receptor, soluble fms-like tyrosine kinase-1 (sFLT-1), across the menstrual cycle in normal ovulating women in relation to reproductive hormones to identify the utility of VEGF and sFLT-1 as peripheral biomarkers of endometrial remodeling. METHODS Ninety-six healthy, regularly menstruating ovulatory women, aged 18-44 years, enrolled in the BioCycle Study, a prospective cohort study at a U.S. academic research center. Vascular endothelial growth factor and sFLT-1 were measured in concurrently collected plasma, serum, and urine up to eight times across a single cycle. Reproductive hormones were measured in serum. Mean concentrations of VEGF and sFLT-1 were compared across phases of the cycle, and correlations between specimen types were calculated. Harmonic models estimated associations between VEGF and sFLT-1 and characteristics of hormonal patterns. RESULTS No variation in VEGF or sFLT-1 levels were detected over the menstrual cycle. Median (25th percentile, 75th percentile) concentrations of VEGF during the menstrual cycle were 31.2 pg/mL (24.1, 56.9) in plasma, 194.1 pg/mL (125.4, 350.2) in serum, and 101.7 pg/mL (64.2, 165.8) in urine. Plasma and serum measures were consistently correlated, whereas urinary measures were not. Vascular endothelial growth factor was not consistently associated with reproductive hormone concentrations, although sFLT-1 was associated with higher mean and amplitude of estradiol. CONCLUSION Circulating VEGF and sFLT-1 did not vary across the menstrual cycle and therefore are unlikely to be useful peripheral biomarkers of endometrial changes across the menstrual cycle. For studies measuring circulating VEGF for other reasons, plasma may be the preferred medium and timing to menstrual cycle phase need not be considered for reproductive-age women.

Objective To determine whether subfertility in patients with endometriosis is due to impaired endometrial receptivity by comparing pregnancy and live-birth outcomes in women with endometriosis versus two control groups without suspected endometrial factors: noninfertile patients who underwent assisted reproduction to test embryos for a single-gene disorder and couples with isolated male factor infertility. Design Retrospective cohort. Setting Multicenter private practice. Patient(s) All patients aged 24 to 44 years undergoing euploid frozen blastocysts transfer from January 2016 through March 2018. Intervention(s) None. Main Outcome Measure(s) Live birth, clinical pregnancies, pregnancy losses, and aneuploid rates in preimplantation genetic testing for aneuploidy cycles. Result(s) The analysis included 459 euploid frozen embryo transfer cycles among 328 unique patients. There were no differences in clinical pregnancy, pregnancy loss, or live-birth rates in patients with endometriosis compared with both control groups. The aneuploidy rates were lowest in the preimplantation genetic testing for monogenic disorders cohort, and the endometriosis patients had aneuploidy rates similar to those of the male factor infertility patients. Conclusion(s) It is unclear whether endometriosis primarily affects in vitro fertilization outcomes via oocyte quality or the endometrium. By controlling for embryo quality using euploid frozen embryo transfer cycles, we found no difference in pregnancy outcomes in patients with endometriosis compared with patients undergoing treatment for male factor infertility and noninfertile patients.

OBJECTIVE To estimate the risk of a multiple gestation pregnancy in ovarian stimulation intrauterine insemination (IUI) cycles when stratified by patient age and mature follicle number. METHODS We conducted a retrospective cohort study at a single private practice fertility center of IUI cycles performed from 2004 to 2017. Intervention(s) were ovarian stimulation and IUI if postwash total motile sperm count was more than 8 million. Mature follicles were defined as 14 mm or more as measured on the day of ovulation trigger. Main outcomes and measures were rates of clinical pregnancy and multiple gestation. RESULTS We identified 24,649 women who underwent a total of 50,473 IUI cycles. Increasing the number of mature follicles from one to five at the time of IUI in women younger than age 38 years increased the clinical pregnancy rate from 14.6% to 21.9% (adjusted odds ratio [aOR] 1.6, 95% CI 1.4-1.9), almost entirely from a marked increase in multiple gestations per cycle from 0.6% to 6.5% (aOR 9.9, 95% CI 6.9-14.2). There was little increase in singleton pregnancies per IUI (14.1-16.4%) regardless of mature follicle number. The per-pregnancy twin and higher-order multiple gestation risk significantly increased (3.9-23.3%, P

Science, propelled forward by noble aspirations and, at times, human hubris, has the capacity to affect lives and alter the world in unanticipated ways. Even seemingly minor discoveries have repeatedly proven to have far reaching implications that experts within their respective fields could not have predicted. Nuclear technology is both a source of energy and a potential means of annihilation. The internet has both seamlessly connected the world but has also opened society to the misuse and manipulation of information. Both exemplify how new technologies have the potential for positive and negative outcomes that often go beyond what was initially intended. This is not a fault of science and innovation but rather an inherent occupational hazard as new discoveries exist within a gray zone between ignorance and comprehension. These gaps in our knowledge can only be filled over time as our knowledge expands. Innovations that were once seen as fringe, over time, become mainstream and that which was once revolutionary becomes a part of everyday life. Occasionally, a scientific advancement comes along that challenges societal norms and causes us to question what is feasible, acceptable, and ethical. Nowhere in the twenty-first century has this been more evident than within the fields of genetics and genetic engineering. As we gain a deeper understanding of the source code of life, from individual base pairs to epigenetic influences, the implications of new discoveries will go far beyond curing genetic diseases, and the possibilities will be endless. Reproductive endocrinology and infertility (REI) specialists utilize many tools including expanded carrier screening, preimplantation genetic testing, and embryo selection and have become some of the experts at the forefront of the ongoing genetic revolution. Now more than ever, there is a need for REIs to be trained in the fundamentals of genetics, exposed to novel gene sequencing and editing techniques, and involved in the coming ethical discussions in order to be prepared for the genetically engineered future.

With improvement in cancer therapies, there has been an increasing emphasis on survivorship, including options for fertility preservation. Fertility preservation is the process of either protecting or saving gametes or reproductive tissues for potential future procreation. Methods and outcomes of fertility preservation have similarly been rapidly advancing. Before initiation of gonadotoxic therapy, health care providers must consider future fertility of patients and provide options for fertility preservation. Nonetheless, the cost of fertility preservation can be prohibitory. Depending on a patient's state of residence, insurance may be mandated to cover, or offer to cover, the cost of fertility preservation. State legislation continues to change; however, legislation at the federal level has been proposed to make this coverage more cohesive. This commentary reviews current state legislation regarding mandates to cover the cost of fertility preservation for patients at risk for iatrogenic infertility and outlines the importance of developing federal legislation to improve patient access to care.

Objective: Accurate measurement of steroid hormones remains challenging. Mass spectrometry affords a reliable means for quantitating steroid profiles accurately. Our objective was to establish and define (1) the extent of diurnal fluctuations in steroid concentrations that potentially necessitate strict adherence to time of sample acquisition and (2) time-dependent steroid reference intervals. Design: Nine steroid markers were examined in couplets in males and females. Methods: Using isotope dilution high-performance liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis, we developed a multi-steroid profile requiring only a minimal volume of serum (0.1 mL). Couplet (AM and PM) measurements of steroid hormones for 120 healthy females (F) and 62 healthy males (M) were obtained. Patients were recruited from several participating centers. Results: The following diurnal values were noted to be significantly different in both females and males: cortisone, cortisol, corticosterone, 11 deoxycortisol (11 DOC), androstenedione, 17a-hydroxyprogesterone (17 OHP) and dehydroepiandrosterone (DHEA). Testosterone was only found to have significant diurnal variance in males. Progesterone showed no significant difference in AM and PM values for either groups and thus may provide an internal control. Conclusions: When diagnosing endocrine disorders, it is imperative to acknowledge the 24-h diurnal variation of the biochemical steroid markers. We highlight the importance of standardization of collection times and appropriate implementation of reference intervals. Precis: We identify diurnal fluctuations in steroid concentrations with time of day and emphasize the importance of adhering to firm time of sample acquisition. National Center for Advancement of Translational Science (UL1TR001409) United States Department of Health & Human Services National Institutes of Health (NIH) - USA (NCT00428987) National Center for Advancement of Translational Science NIH Intramural Research Grant United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) (ZIEHD008737) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Center for Advancing Translational Sciences (NCATS) (UL1TR001409) CLINICAL CENTER (ZIACL010355)

Premature progesterone (P) elevation was commonly seen in IVF prior to the utilization of GnRH analogues for suppression of endogenous gonadotropin release. The cause and effect of premature P elevation has finally been better elucidated in the past decade. Although still occurring in 5-38% of all IVF cycles, the adverse effects of premature P elevation on pregnancy outcomes are now well known.

PURPOSE: To describe controlled ovarian stimulation (COS) in a population of women with GATA2 deficiency, a genetic bone marrow failure syndrome, prior to allogeneic hematopoietic stem cell transplant METHODS: This is a retrospective case series of nine women with GATA2 deficiency who underwent oocyte preservation at a research institution. Main outcomes measured include baseline fertility characteristics ((antimullerian hormone (AMH) and day 3 follicle-stimulating hormone (FSH) and estradiol (E2)) and total doses of FSH and human menopausal gonadotropins (HMG), E2 on day of trigger, and total number of metaphase II oocytes retrieved. RESULTS: The mean age was 24 years [16–32], mean AMH was 5.2 ng/mL [0.7–10], and day 3 mean FSH was 5.1 U/L [0.7–8.1], and E2 was 31.5 pg/mL [

Background Isolated absent thelarche is a rare condition that is infrequently reviewed in the literature. Case A 28-year-old woman with neurofibromatosis type 1 and acromegaly presented with absent breast development despite hormone therapy. Examination noted a normally developed woman with acromegalic features and Tanner stage I breasts. Hormone studies and karyotype were normal. Magnetic resonance imaging of the patient's brain demonstrated a voluminous pituitary. Chromosome microarray analysis diagnosed the neurofibromatosis 1 microdeletion syndrome. Breast ultrasonography and surgical consultation were offered. Conclusions Neither neurofibromatosis type 1, acromegaly, nor neurofibromatosis 1 microdeletion syndrome are linked to absent thelarche. After attempting hormone therapy, patients with absent thelarche should be evaluated for congenital breast anomalies, estrogen receptor abnormalities, or gene defects. Psychological and surgical consultation should also be offered.

Objective: Use of frozen sperm in non-male factor infertility is often needed in donor cycles. Most studies to date examining outcomes of fresh vs frozen sperm are unable to control for oocyte quality. Studies examining sibling oocytes represent a unique model to control for oocyte quality. A recent small study using this model found worse outcomes in the frozen group. We sought to evaluate, in a large cohort, if fresh and frozen ejaculated sperm are associated with similar pregnancy outcomes by analyzing paired donor egg recipient (DER) cycles. Materials and Methods: Retrospective cohort study from 2016-2019 at a large fertility center. Patients who underwent DER cycles where oocytes were split between two couples and one couple used fresh sperm and the other used frozen sperm were included. All patients with uterine factor, male factor or surgically obtained sperm were excluded. Primary outcome was Ongoing pregnancy/Live birth rate (OPR). Secondary outcome included clinical pregnancy rate (CPR) and miscarriage rate. GEE analysis was performed to control for confounding factors and donors providing oocytes to both study cohorts. Results: 1255 donor oocytes cycles were screened. A total of 205 unique oocytes donors were identified with oocytes inseminated with discrepant sperm in different recipient cycles. There were 698 recipient transfer cycles, 405 fresh and 293 frozen. Cohorts were similar in baseline characteristics (table 1). There were no differences in OPR/LBR with fresh vs frozen sperm (53.6% vs 55.6%, p=0.7) or clinical pregnancies (66.4% vs 63.5%, p=0.4). Spontaneous miscarriage (