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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.

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.

Introduction Total pancreatectomy with autologous islet transplant (TPAIT) is indicated for patients with chronic pancreatitis to improve quality of life while reducing complications from hypoglycemia. Continuous glucose monitoring (CGM) was used to assess overall islet function and the incidence of hypoglycemia pre- and post-operatively. Methods Nineteen patients who underwent TPAIT at a single center from 2018-2020 were included. Pre-operatively, patients were defined by diabetic status. HbA1c, stimulated C-peptide, and CGM were used to characterize glycemic function. Results Pre-operatively, 3 patients had diabetes, and 16 patients did not have diabetes. 8 out of 16 non-diabetic patients were insulin independent (50%). Of 6 non-diabetic patients with > 10% hypoglycemia on pre-operative CGM, 33% were insulin-independent post-operatively (p = 0.3). Of non-diabetic patients with ≥ 80% time in the euglycemic range, 62% were insulin-independent post-operatively (p = 0.2). For patients without diabetes, the median percent time in hypoglycemic range was reduced from 8% to 1% (p = 0.001). Delta C-peptide had a positive correlation with islet yield (p = 0.03). Discussion Conventional evaluation of TPAIT patients assesses primarily beta cell function. As pancreatogenic diabetes is concerning principally for the risk of hypoglycemia, assessment of alpha cell function can improve the quality of care. CGM better captures islet function and increases the identification of hypoglycemia. This article is protected by copyright. All rights reserved.

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.

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

Background- Patients treated for chronic lymphocytic leukemia are frequently administered ibrutinib. Ibrutinib inhibits Bruton’s tyrosine kinase, blocks the B-cell receptor signaling pathway, thereby reducing downstream effects such as proliferation; effectively treating the malignancy. Adverse events such as bleeding have been reported and are suspected to be caused by inhibition of kinases in the platelet aggregation pathway. Clinical Case- A 60-year-old man with chronic lymphocytic leukemia, treated with ibrutinib for five months, was diagnosed with pituitary apoplexy and consequent panhypopituitarism. He presented with a severe headache one month prior to diagnosis. At this time, a non-contrast head CT was interpreted as unremarkable. On second presentation one month later, studies showed a serum sodium of 116 mmol/L (135-145 mmol/L), glucose of 43 mg/dL (65-179 mg/dL), and blood pressure of 95/52. An MRI brain demonstrated an enlarged pituitary with areas of intrinsic T1 hyperintense signal noted within the sella turcica suggestive of blood products. Serum cortisol rose from 0.3 to 8.9 ug/dL (4.5-22.7 ug/dL) one hour after IV injection of 250 mcg cosyntropin. Paired ACTH was < 5 pg/mL (7.2-63 pg/mL). Hydrocortisone was started and blood pressure, sodium, and glucose normalized. LH was 0.9 mIU/mL (3-10 mIU/mL), FSH was 4.7 mIU/mL (1.6-9.7 mIU/mL), and total testosterone was < 0.7 ng/dL (240-950 ng/dL). TSH was 0.115 uIU/mL (0.6-3-3 uIU/mL) with FT4 of 0.84 ng/dL (0.71-1.4 ng/dL). Prolactin was 2.4 ng/mL (4-18 ng/mL) and IGF-1 Z score was -1.28 (-2.0-2.0). Replacement levothyroxine and testosterone were started. Oncology stopped ibrutinib and switched therapy to rituximab and venetoclax. A pituitary MRI two months later showed significant improvement of the T1 hyperintensity (blood products) and a 1.1 cm adenoma was found. During the entire course of his illness his platelet counts ranged from 275 to 431 109/L (150-440 109/L). His INR was 1.14 and PT 13.2 sec (10.2-13.2 sec). He has recovered well on hormone replacement. Discussion- Pituitary apoplexy often has underlying risk factors, including pituitary adenomas and coagulopathies. To our knowledge apoplexy has not been reported in patients taking ibrutinib, though bleeding and platelet dysfunction have been well described. Knowledge of the possible side effects of newer anti-cancer drugs is increasingly important for the endocrinologist.

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)

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 (

Endometriosis is a chronic medical condition that affects around 6% to 10% of reproductive age women. Pelvic pain, dysmenorrhea, and infertility are the most common presenting symptoms. The disease is characterized by estrogen-dependent growth of the endometrial glands and stroma outside the endometrial cavity. The diagnosis requires a high degree of suspicion and can be only confirmed on histopathology. Treatment includes medical and surgical options. Both hormonal and nonhormonal medical options are available and are tried at first with a goal to control pain and stop the growth of the endometriotic lesions. Nonsteroidal anti-inflammatory drugs, oral contraceptive pills, gonadotropin-releasing hormone (GnRH) agonists, aromatase inhibitors are some of the commonly used medications. With more research on the molecular and biochemical aspects of endometriosis, newer targets of therapy are being developed like selective progesterone receptor modulators, antiangiogenic factors and immunomodulators. In women who do not respond to medical therapy or have severe symptoms, surgical excision of the endometrial lesions and adhesions is often helpful and offers confirmatory diagnosis by histopathology.

Epigenetic influences have been postulated to affect the course of endometriosis. DNA methyltransferases, estrogen and progesterone receptors, micro-RNAs, and histone deacetylators, have shown differential expression in endometriosis compared with normal endometrium. Others such as aromatase, Steroid Factor-1, COX-2, and Homeobox A10 also have epigenetic modifications in endometriosis. Limitations in this area of research include heterogeneity in study design, patient populations, and methods of analysis. Larger, controlled studies are needed. Future targeted uses of this work may include using methylomes to noninvasively diagnose endometriosis, or targeting histone-deacetylase inhibitors for treatment.

Approximately 30% to 50% of women that have the diagnosis of endometriosis also struggle with infertility. Twenty five percent to 50% of women diagnosed with infertility also have endometriosis, but the endometriosis may not be severe enough to be the primary etiology of infertility. White women have been reported to be more likely than African American women to have endometriosis. In addition, risk factors for endometriosis include below average body mass index, smoking, and alcohol use. Below is a discussion regarding the various ways in which endometriosis decreases fecundity and also discusses potential outcomes of fertility treatments regarding endometriosis.

Endometriosis is a complex, puzzling disease in women of reproductive age. The exact cause of the disease is unknown; however, different genetic and environmental factors contribute to the evolution of the disorder. Further investigation has led to the discovery of inheritance as a complex genetic trait. Candidate genes were identified to isolate regions of genes that affect disease risk. Additional linkage studies have been performed to map specific genes along the entire genome. Recent advances to determine the genetic component of endometriosis include genome-wide association studies. This chapter focuses on different approaches to identify the genetic links of endometriosis and its pathogenesis.

STUDY QUESTION Do donor oocyte recipients benefit from preimplantation genetic testing for aneuploidy (PGT-A)? SUMMARY ANSWER PGT-A did not improve the likelihood of live birth for recipients of vitrified donor oocytes, but it did avoid embryo transfer in cycles with no euploid embryos. WHAT IS KNOWN ALREADY Relative to slow freeze, oocyte vitrification has led to increased live birth from cryopreserved oocytes and has led to widespread use of this technology in donor egg IVF programs. However, oocyte cryopreservation has the potential to disrupt the meiotic spindle leading to abnormal segregation of chromosome during meiosis II and ultimately increased aneuploidy in resultant embryos. Therefore, PGT-A might have benefits in vitrified donor egg cycles. In contrast, embryos derived from young donor oocytes are expected to be predominantly euploid, and trophectoderm biopsy may have a negative effect relative to transfer without biopsy. STUDY DESIGN, SIZE, DURATION This is a paired cohort study analyzing donor oocyte-recipient cycles with or without PGT-A performed from 2012 to 2018 at 47 US IVF centers. PARTICIPANTS/MATERIALS, SETTING, METHODS Vitrified donor oocyte cycles were analyzed for live birth as the main outcome measure. Outcomes from donors whose oocytes were used by at least two separate recipient couples, one couple using PGT-A (study group) and one using embryos without PGT-A (control group), were compared. Generalized estimating equation models controlled for confounders and nested for individual donors contributing to both PGT-A and non-PGT-A cohorts, enabling a single donor to serve as her own control. MAIN RESULTS AND THE ROLE OF CHANCE In total, 1291 initiated recipient cycles from 223 donors were analyzed, including 262 cycles with and 1029 without PGT-A. The median aneuploidy rate per recipient was 25%. Forty-three percent of PGT-A cycles had only euploid embryos, whereas only 12.7% of cycles had no euploid embryos. On average 1.09 embryos were transferred in the PGT-A group compared to 1.38 in the group without PGT-A (P LIMITATIONS, REASONS FOR CAUTION Pooled clinical data from 47 IVF clinics introduced PGT-A heterogeneity as genetic testing were performed using different embryology laboratories, PGT-A companies and testing platforms. WIDER IMPLICATIONS OF THE FINDINGS PGT-A testing in donor oocyte-recipient cycles does not improve the chance for live birth nor decrease the risk for miscarriage in the first transfer cycle but does increase cost and time for the patient. Further studies are required to test if our findings can be applied to the young infertility patient population using autologous oocytes. STUDY FUNDING/COMPETING INTEREST(S) No external funding was used for this study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A.

Objective To estimate the effect of daily 81 mg low-dose aspirin (LDA) on menstrual cycle length and hormone profiles. Design Secondary analysis of a trial evaluating the effect of daily LDA or placebo on live birth among women with one or two previous pregnancy losses. Setting University medical centers. Patient(s) A total of 915 regularly menstruating women who had at least one menstrual cycle (3,190 total cycles) in which pregnancy did not occur. Intervention(s) Randomized allocation to LDA versus placebo. Main Outcome Measure(s) Menstrual cycle length and follicular and luteal phases were measured. Urinary pregnanediol glucuronide, follicle-stimulating hormone, luteinizing hormone, and estrone-3-glucuronide were assessed up to six times during the first two cycles. Generalized estimating equations estimated relative risk of short ( 75th percentile: ≥32 days) versus normal cycle length. Linear mixed models estimated mean hormone level differences with weights used to account for multiple cycles contributed per participant. Result(s) There were no significant differences in total menstrual cycle, follicular phase, or luteal phase length between LDA and placebo groups. LDA posed no greater risk of having a short versus normal-length or long versus normal-length follicular phase, or having a short versus normal-length or long versus normal-length luteal phase. There were no significant differences in hormone levels across the menstrual cycle between the LDA and placebo groups. Conclusion(s) Daily LDA use did not result in any changes to menstrual cycle, follicular phase, or luteal phase length or hormone levels across the menstrual cycle compared with placebo. Clinical Trial Registration Number NCT00467363

Objectives To identify uterine measurements that are reliable and accurate to distinguish between T-shaped and normal/arcuate uterus, and define T-shaped uterus, using Congenital Uterine Malformation by Experts (CUME) methodology, which uses as reference standard the decision made most often by several independent experts. Methods This was a prospectively planned multirater reliability/agreement and diagnostic accuracy study, performed between November 2017 and December 2018, using a sample of 100 three-dimensional (3D) datasets of different uteri with lateral uterine cavity indentations, acquired from consecutive women between 2014 and 2016. Fifteen representative experts (five clinicians, five surgeons and five sonologists), blinded to each others' opinions, examined anonymized images of the coronal plane of each uterus and provided their independent opinion as to whether it was T-shaped or normal/arcuate; this formed the basis of the CUME reference standard, with the decision made most often (i.e. that chosen by eight or more of the 15 experts) for each uterus being considered the correct diagnosis for that uterus. Two other experienced observers, also blinded to the opinions of the other experts, then performed independently 15 sonographic measurements, using the original 3D datasets of each uterus. Agreement between the diagnoses made by the 15 experts was assessed using kappa and percent agreement. The interobserver reliability of measurements was assessed using the concordance correlation coefficient (CCC). The diagnostic test accuracy was assessed using the area under the receiver-operating-characteristics curve (AUC) and the best cut-off value was assessed by calculating Youden's index, according to the CUME reference standard. Sensitivity, specificity, negative and positive likelihood ratios (LR- and LR+) and post-test probability were calculated. Results According to the CUME reference standard, there were 20 T-shaped and 80 normal/arcuate uteri. Individual experts recognized between 5 and 35 (median, 19) T-shaped uteri on subjective judgment. The agreement among experts was 82% (kappa = 0.43). Three of the 15 sonographic measurements were identified as having good diagnostic test accuracy, according to the CUME reference standard: lateral indentation angle (AUC = 0.95), lateral internal indentation depth (AUC = 0.92) and T-angle (AUC = 0.87). Of these, T-angle had the best interobserver reproducibility (CCC = 0.87 vs 0.82 vs 0.62 for T-angle vs lateral indentation depth vs lateral indentation angle). The best cut-off values for these measurements were: lateral indentation angle = 7 mm (sensitivity, 95%; specificity, 77.5%; LR+, 4.2; LR-, 0.06) and T-angle = 7 mm, lateral indentation angle