High estradiol levels in fresh embryo transfer cycles are not associated with detrimental impact on birth outcomes.

PURPOSE: There is an unclear relationship between estradiol levels and fresh embryo transfer (ET) outcomes. We determined the relationship between estradiol on the day of trigger, in fresh ET cycles without premature progesterone elevation, and good birth outcomes (GBO). METHODS: We identified autologous fresh ET cycles from 2015 to 2021 at multiple clinics in the USA. Patients with recurrent pregnancy loss, uterine factor, and elevated progesterone on the day of trigger (progesterone > 2 ng/mL or 3-day area under the curve > 4.5 ng/mL) were excluded. The primary outcome was GBO (singleton, term, live birth with appropriate weight). Log-binomial generalized estimating equations determined the likelihood of outcomes. RESULTS: Of 17,608 fresh ET cycles, 5025 (29%) yielded GBO. Cycles with estradiol ≥ 4000 pg/mL had a greater likelihood of GBO compared to cycles < 1000 pg/mL (aRR = 1.32, 95% CI 1.13-1.54). Pairwise comparisons of estradiol between < 1000 pg/mL versus 1000-1999 pg/mL and 1000-1999 pg/mL versus 2000-2999 pg/mL revealed a higher likelihood of GBO with higher estradiol (aRR 0.83, 95% CI 0.73-0.95; aRR 0.91, 95% CI 0.85-0.97, respectively). Comparisons amongst more elevated estradiol levels revealed that the likelihood of GBO remained similar between groups (2000-2999 pg/mL versus 3000-3999 pg/mL, aRR 1.04, 95% CI 0.97-1.11; 3000-3999 pg/mL versus ≥ 4000 pg/mL, aRR 0.96, 95% CI 0.9-1.04). CONCLUSION: In fresh ET cycles, higher estradiol levels were associated with an increased prevalence of GBO until estradiol 2000-2999 pg/mL, thereafter plateauing. In fresh ET candidates, elevated estradiol levels should not preclude eligibility though premature progesterone rise, and risk of ovarian hyperstimulation syndrome must still be considered.

Use of low dose vaginal misoprostol in office hysteroscopy: a pre-post interventional study.

A pre-post interventional study of patients undergoing office hysteroscopy alone and in combination with endometrial biopsy was performed during October 2015-March 2018 to evaluate the effect of low dose vaginal misoprostol on patient's pain. Pain scores were assessed using the visual analog scale at the completion of the procedure. There were 646 patients included in the study. Of these, 462 had office hysteroscopy alone; 206 (44.6%) received 50 mcg of vaginal misoprostol the night prior to the procedure and the remaining 256 (55.4%) patients had no cervical ripening. The reported pain score following hysteroscopy was significantly lower among patients who received misoprostol [4(0-10) vs. 5(0-10); p=.001]. Most patients (78.2%) did not report any misoprostol related side effects. Of the 184 patients who underwent a combination of office hysteroscopy and endometrial biopsy, 97 (52.7%) received pre-procedure vaginal misoprostol while 87 (47.3%) did not. Post procedure pain was independent of pre-treatment with vaginal misoprostol (6.3 ± 2.7 vs. 6.6 ± 2.7; p = .54).Impact statementWhat is already known on this subject? Office hysteroscopy and endometrial biopsy is increasingly performed for evaluation of various gynaecologic conditions, however, patients' perceived pain at the time of procedure may lead to incomplete procedures. Various doses of misoprostol have been tested to reduce patients' pain, however none lower than 200 mcg vaginally, and at these doses, side effects are reported.What the results of this study add? To date, there is a scarcity of published data on the use of low dose misoprostol (50 mcg) in gynaecologic procedures. Our study found that the use of low dose vaginal misoprostol prior to office hysteroscopy is associated with lower reported pain and tenaculum utilisation during the procedure. However, vaginal misoprostol prior to successive office hysteroscopy and endometrial biopsy failed to decrease the reported pain, and the overall pain score was higher than hysteroscopy alone.What the implications are of these findings for clinical practice and/or further research? The use of low dose vaginal misoprostol (50 mcg) the evening prior to office hysteroscopy is associated with lower reported pain and tenaculum utilisation and is not associated with significant side effects. Therefore, 50 mcg of misoprostol could be used in clinical practice as a method to reduce patients' reported pain during office hysteroscopy.

Association between Preoperative Adenomyosis Detection Rate during Pelvic Ultrasonography and the Specialty of the Reading Physician.

STUDY OBJECTIVE: To compare the detection rate of adenomyosis when ultrasound is performed by a radiologist compared with a gynecologic expert sonologist. DESIGN: A retrospective, single-center study. SETTING: A university teaching hospital. PATIENTS: All women above 18 years of age with a positive histopathology diagnosis of adenomyosis obtained in a hysterectomy specimen from October 1, 2011, to October 1, 2017, were screened for inclusion. Cases without a preoperative pelvic ultrasound report, those with coexisting premalignant/malignant conditions, and patients presenting to the clinic with symptoms other than abnormal uterine bleeding, dysmenorrhea, or abdominal pain were excluded. A total of 412 cases were included in the final analysis. MEASUREMENTS AND MAIN RESULTS: The preoperative ultrasound was performed by a radiologist in 241 patients (59%) and by an expert gynecologic sonologist in 171 patients (42%). Patients' age, body mass index, race, ethnicity, parity, and history of prior cesarean section were comparable between the 2 groups. The adenomyosis detection rate was significantly higher in the expert gynecologic sonologist group compared with radiologists (95 [56%] vs 29 [12%], p <.01). After controlling for patients' race, body mass index, prior cesarean sections, and presence of myomas using multivariable logistic regression, gynecologic expert sonologists were 7.8 times more likely to detect adenomyosis than radiologists (odds ratio = 7.84; 95% confidence interval, 4.58-13.44). Regardless of medical specialty, the presence of myomas significantly decreased the detection of adenomyosis compared with the absence of myomas (odds ratio = 0.23; 95% confidence interval, 0.13-0.39). CONCLUSION: The detection rate of adenomyosis was significantly higher when ultrasound was performed by expert gynecologic sonologists compared with radiologists. The presence of myomas significantly decreased detection rates regardless of specialty. Ultrasound evaluation for detecting adenomyosis should be preferentially performed by gynecologic expert sonologists.

Laparoscopic Entry Technique Using a Veress Needle Insertion with and without Concomitant CO2 Insufflation: A Randomized Controlled Trial.

STUDY OBJECTIVE: To compare the time and number of attempts needed for successful Veress needle entry during laparoscopic surgery using concomitant versus subsequent CO2 insufflation approaches. DESIGN: Randomized controlled trial. SETTING: University teaching hospital. PATIENTS: One hundred consecutive patients scheduled for laparoscopic surgery by 2 high-volume laparoscopic surgeons were screened and randomized, and 95 of these were included in the final analysis. Ninety (45 in each group) was the precalculated priori number of patients needed to detect a 50% difference in the time (seconds) to obtain adequate insufflation with 90% power and alpha of 5%. INTERVENTIONS: Patients were randomized to either Veress needle entry with concomitant (Con) or subsequent (Sub) CO2 insufflation. MEASUREMENTS AND MAIN RESULTS: Forty-six patients were randomized to the Con group and 49 to the Sub group. Patient age, body mass index, prior surgical history, presence of adhesions, and type of procedure performed were similar between both groups. The median time required for adequate insufflation in the Con group was 103.5 seconds (Q1-Q3, 80.0-130.0) compared with 113.0 seconds (Q1-Q3, 102.0-144.0) in Sub group (p = .16). Approximately 89% (95% confidence interval, 80.1%-98.1%) of patients in Con group achieved successful entry in the first attempt compared with only 67% (95% confidence interval, 54.2%-80.0%) in Sub group (p = .01). The incidence of preperitoneal insufflation and failed entry was comparable between the 2 groups. No patient developed solid organ, visceral, or vascular injuries; gas embolism; or case conversion to laparotomy in relation to the Veress needle entry technique. CONCLUSION: Veress needle entry with concomitant CO2 insufflation was associated with a higher rate of successful entry during the first attempt of Veress needle insertion. The total time required for insufflation and rates of complications between the 2 techniques were similar.

Contemporary management of adnexa at the time of benign hysterectomy: a review of the literature.

Ovarian cancer is the leading cause of Gynecological cancer related mortality in the USA. Due to the absence of an effective screening method, concomitant adnexal management during hysterectomy or other pelvic surgeries is a prime consideration. Bilateral salpingo-oophorectomy (BSO) offers the benefit of eliminating the risk of ovarian cancer however it leads to surgical menopause with unfavourable overall health outcomes. With the latest verification that serous tubal intraepithelial carcinoma detected in the distal fimbriated end of the fallopian tube being the precursor of Type 2 ovarian cancers, there is an increased trend of performing bilateral salpingectomy (BS) as a risk reduction strategy for ovarian cancer. Women with a high risk for ovarian cancer due to familial or genetic mutations and those diagnosed with endometriosis need particular attention while planning adnexal management during hysterectomy. Physician and patient's shared decision-making regarding adnexal management during benign hysterectomy taking into consideration the route of hysterectomy is an important portion of pre-operative planning. The objective of this article is to understand the current trends of BSO and BS during benign hysterectomy and appreciate the pros and cons to aid in pre-operative counselling of patients.

National rates, trends and determinants of inpatient surgical management of tubal ectopic pregnancy in the United States, 1998-2011.

AIM: To describe the frequency and temporal trends of inpatient hospitalization for tubal ectopic pregnancy as well as patients' characteristics, determinants and the current national trends in surgical management of ectopic pregnancy. METHODS: We conducted a retrospective, cross-sectional analysis of patients who were treated for tubal ectopic pregnancy in an inpatient hospital setting in the United States from 1998 to 2011 using data from the Nationwide Inpatient Sample databases. National frequency and significant changes in the rate of surgical management of tubal ectopic pregnancy in the inpatient setting are described. RESULTS: The study included 334 639 tubal ectopic pregnancies for women aged 18-50 in the United States from 1998 to 2011. The rate of tubal ectopic pregnancy (per 10 000 maternal admissions) decreased from 77.2 in 1998 to 40.5 in 2011. The proportion of tubal ectopic pregnancies for which salpingostomy was performed decreased from 17.0% in 1998 to 7.0% in 2011, while the rate of salpingectomy increased from 69.3% in 1998 to 80.9% in 2011. The temporal change in surgical choice was not different in states with comprehensive in vitro fertilization insurance mandates. CONCLUSION: The rate of tubal ectopic pregnancy managed in the inpatient setting in the United States decreased 5% annually between 1998 and 2011. The rate of salpingectomies performed annually increased whereas that of salpingostomy decreased over time. The surgical approach selected for the management of tubal ectopic pregnancies was not influenced by a state's in vitro fertilization mandate status.

Trends of Bilateral Salpingectomy During Vaginal Hysterectomy With and Without Laparoscopic Assistance Performed for Benign Indications in the United States.

STUDY OBJECTIVE: To estimate the recent temporal trends of concurrent bilateral salpingectomy (BS) during vaginal hysterectomy (total vaginal hysterectomy [TVH] and laparoscopic-assisted vaginal hysterectomy [LAVH]) in the United States. DESIGN: A cross-sectional analysis was conducted using data from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample, including all female patients 18 years and older whose inpatient discharge record indicated a TVH or LAVH performed for benign indications between January 1, 1998, and December 31, 2011. Joinpoint regression was used to identify statistically significant changes in overall and subgroup temporal trends of TVH and LAVH as well as concomitant BS during the 14-year study period (Canadian Task Force Classification II). SETTING: Not applicable. PATIENTS: All patients who underwent TVH and LAVH from 1998 to 2011 registered in the Healthcare Cost and Utilization Project Nationwide Inpatient Sample database. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Regarding TVH, between 1998 and 2001, there was a steep negative trend with an annual percentage change of -5.2 (95% confidence interval [CI], -8.8 to -2.2). From 2001 to 2011, the negative trend was still observed but with a more gradual 2% annual decrease (95% CI, -2.4 to -1.3). Conversely, the rate of LAVH increased at a rate of 4.4% each year (95% CI, 3.7-5.0). From 1998 to 2004, the national rate of BS during TVH increased sharply with an annual increase of 42.8% (95% CI, 22.7-66.3). Beginning in 2004, the BS rate during TVH decreased and remained stable. During LAVH, the rate of concomitant BS increased an estimated 15% each year during the entire study period (95% CI, 11.9-17.8). CONCLUSION: The proportion of annual LAVH with concomitant BS procedures performed across the nation is on the rise while TVH is declining with a stable rate of concomitant BS.

National trends of adnexal surgeries at the time of hysterectomy for benign indication, United States, 1998-2011.

OBJECTIVE: We sought to investigate the most recent national trends of bilateral salpingectomy (BS) and bilateral salpingo-oophorectomy (BSO) at the time of hysterectomy performed for benign indications. STUDY DESIGN: We conducted a national cross-sectional analysis of all inpatient discharges for women aged ≥18 years who underwent a hysterectomy for benign indications from 1998 through 2011 using the largest publicly available all-payer inpatient database in the United States. We scanned International Classification of Diseases, Ninth Revision codes for an indication of specific bilateral adnexal surgeries, including BSO and BS. Joinpoint regression was used to characterize and estimate 14-year national trends in performing BSO and BS at the time of hysterectomy for benign indications, overall and in population subgroups. RESULTS: During the study period, there were approximately 428,523 inpatient hysterectomy procedures performed annually for benign indications. Of these, >53% had no adnexal surgery performed during the same hospitalization, whereas 43.7% and 1.3% of those discharges had BSO and BS procedures, respectively. The rate of BSO was directly correlated with increasing age for patients <65 years. Conversely, we observed an inverse relationship between BS and patient age, with the BS rate among women aged <25 years twice that of women aged ≥45 years. From 1998 through 2001, there was a 2.2% increase in the rate of BSO per year (95% confidence interval, 0.4-4.0); however, this was followed by a consistent 3.6% (95% confidence interval, -4.0 to -3.3) annual decline in the BSO rate, from 49.7% in 2001 to 33.4% in 2011. National rates of BS among women undergoing hysterectomy for benign indications increased significantly throughout the study period, with an estimated 8% annual increase from 1998 through 2008, followed by a sharp 24% increase annually during the last 4 years of the study period. The BS rate nearly quadrupled in 14 years. CONCLUSION: The type of adnexal surgery performed concomitantly with hysterectomy for benign indications has undergone a significant shift since 2001. Significantly more BS and less BSO procedures are being performed among gynecologic surgeons in the United States.

The impact of supraphysiologic serum estradiol levels on peri-implantation embryo development and early pregnancy outcome following in vitro fertilization cycles.

PURPOSE: To determine the impact of elevated serum estradiol levels (EE2-defined as levels > 90th percentile) on the day of hCG administration during IVF on oocyte fertilization, embryo development, implantation, clinical pregnancy and miscarriage rates. METHODS: A total of 2,995 consecutive IVF cycles in 1,889 patients with non-donor oocyte retrieval resulting in fresh embryo transfer between 1/1/2005 and 12/31/2011 were analyzed. Cycles were stratified by serum E2 level on the day of hCG administration into those with levels >90th percentile and ≤ 90th percentile. Rates of normal fertilization, embryo development, positive pregnancy test, implantation, clinical pregnancy and spontaneous miscarriage were compared. RESULTS: Serum estradiol above the 90th percentile on the day of hCG administration was associated with a significantly lower rate of normal fertilization (68.6 ± 20 vs. 71.6 ± 21, p = 0.02) when compared with patients with a lower serum estradiol threshold. The proportion of embryos that progressed from 2PN to 6-8 cell on day 3 was not different between the two groups. Although rates of positive pregnancy test (55.2 % vs. 57 %), implantation (26.4 % vs. 28.5 %) and clinical pregnancy (45.5 % vs. 49.4 %) were lower in patients with a higher estradiol threshold, these differences were not statistically significant. Similarly, there was no difference in the spontaneous miscarriage rates between the two groups (8.4 % vs. 7.1 %). CONCLUSIONS: Serum estradiol levels above the 90th percentile on the day of hCG administration is associated with lower oocyte fertilization rate; however, such levels do not impact embryo development, implantation, clinical pregnancy or spontaneous miscarriage rates.

Total laparoscopic hysterectomy in the obese patient.

Obesity is a challenging health problem that affects surgical decision-making. Obesity has also been associated with an increase in the perioperative complication rate in open abdominal hysterectomy and can increase the level of difficulty in performing a vaginal hysterectomy. Total laparoscopic hysterectomy (TLH) is a route that can offer advantages in obese patients including smaller incisions that are less likely to become infected as well as less post-operative pain and good visualization. With appropriate perioperative planning and techniques, excellent outcomes can be achieved.

Beyond the surface: Does stage I-II endometriosis impact fertility? Exploring the challenges of mild disease.

Endometriosis is one of the most common gynecologic conditions that women face throughout their lives. Despite advances in technology, diagnosis and treatment of this relapsing and remitting condition is still challenging for many women. This review focuses on literature pertaining to minimal/mild (stage I/II) endometriosis and its impact on fertility. The effectiveness of medical interventions to improve infertility and obstetric outcomes in both natural and assisted reproductive technologies cycles remains debated. The recent ESHRE guidelines suggests that operative laparoscopy could be considered for rASRM stage I/II endometriosis as it improves ongoing pregnancy rates.

Dysregulated expression of GATA2 and GATA6 transcription factors in adenomyosis: implications for impaired endometrial receptivity.

OBJECTIVE: To study the effect of adenomyosis on the localized expression of the GATA binding proteins 2 and 6 (GATA2 and GATA6) zinc-finger transcription factors that are involved in proliferation of hematopoietic and endocrine cell lineages, cell differentiation, and organogenesis, potentially leading to impaired endometrial implantation. DESIGN: Laboratory based experimental study. SETTING: Academic hospital and laboratory. PATIENTS: Human endometrial stromal cells (HESCs) of reproductive age patients, 18-45 years of age, with adenomyosis were compared with patients with no pathology and leiomyomatous uteri as controls (n = 4 in each group, respectively). Additionally, midsecretory phase endometrial sections were obtained from patients with adenomyosis and control patients with leiomyoma (n = 8 in each group, respectively). INTERVENTIONS: GATA2 and GATA6 immunohistochemistry and H-SCORE were performed on the midsecretory phase endometrial sections from adenomyosis and leiomyoma control patients (n = 8 each, respectively). Control and adenomyosis patient HESC cultures were treated with placebo or 10-8 M estradiol (E2), or decidualization media (EMC) containing 10-8 M E2, 10-7 M medroxyprogesterone acetate, and 5 × 10-5 M cAMP for 6 and 10 days. Additionally, control HESC cultures (n = 4) were transfected with scrambled small interfering RNA (siRNA) (control) or GATA2-specific siRNAs for 6 days while adenomyosis HESC cultures (n = 4) were transfected with human GATA2 expression vectors to silence or induce GATA2 overexpression. MAIN OUTCOME MEASURES: Immunohistochemistry was performed to obtain GATA2 and GATA6 H-SCORES in adenomyosis vs. control patient endometrial tissue. Expression of GATA2, GATA6, insulin-like growth factor-binding protein 1 (IGFBP1), prolactin (PRL), progesterone receptor (PGR), estrogen receptor 1 (ESR1), leukemia inhibitory factor (LIF), and Interleukin receptor 11 (IL11R) messenger RNA (mRNA) levels were analyzed using by qPCR with normalization to ACTB. Silencing and overexpression experiments also had the corresponding mRNA levels of the above factors analyzed. Western blot analysis was performed on isolated proteins from transfection experiments. RESULTS: Immunohistochemistry revealed an overall fourfold lower GATA2 and fourfold higher GATA6 H-SCORE level in the endometrial stromal cells of patients with adenomyosis vs. controls. Decidual induction with EMC resulted in significantly lower GATA2, PGR, PRL and IGFBP1 mRNA levels in HESC cultures from patients with adenomyosis patient vs. controls. Leukemia inhibitory factor and IL11R mRNA levels were also significantly dysregulated in adenomyosis HESCs compared with controls. . Silencing of GATA2 expression in control HESCs induced an adenomyosis-like state with significant reductions in GATA2, increases in GATA6 and accompanying aberrations in PGR, PRL, ESR1 and LIF levels. Conversely, GATA2 overexpression via vector in adenomyosis HESCs caused partial restoration of the defective decidual response with significant increases in GATA2, PGR, PRL and LIF expression. CONCLUSION: In-vivo and in-vitro experiment results demonstrate that there is an overall inverse relationship between endometrial GATA2 and GATA6 levels in patients with adenomyosis who have diminished GATA2 levels and concurrently elevated GATA6 levels. Additionally, lower GATA2 and higher GATA6 levels, together with aberrant levels of important receptors and implantation factors, such as ESR1, PGR, IGFBP1, PRL, LIF, and IL11R mRNA in HESCs from patients with adenomyosis or GATA2-silenced control HESCs, support impaired decidualization. These effects were partially restored with GATA2 overexpression in adenomyosis HESCs, demonstrating a potential therapeutic target.

The effect of trophectoderm biopsy for preimplantation genetic testing on fetal birth weight and preterm delivery.

BACKGROUND: Preimplantation genetic testing for aneuploidy (PGT-A) is used as part of in-vitro-fertilization (IVF) to assist in selection of euploid embryos, which involves performing trophectoderm biopsy. The effect of possible trauma caused by biopsy and the implication on pregnancy is unknown. Hence, the objective of the study was to determine if embryo biopsy for PGT-A affects birth weight or preterm birth rate. METHODS: Using National Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) data, we identified 6352 cycles which had single embryo transfer (SET) and a singleton live birth following frozen embryo transfer (FET) between 2014 and 2015. RESULTS: From the initial cohort of 25,121 fresh stimulation cycles, 6352 cycles were included who had a singleton live birth following FET. A total of 3482 (54.8%) had PGT-A confirmed euploid embryos and 2870 (45.2%) had embryos selected based on morphology for transfer. No difference in birthweight (g) was noted when FET was performed using PGT-A confirmed euploid embryos as compared to non-tested morphologically selected embryos (3370.7 vs. 3354.5, adjusted regression coefficient 11.4; 95% CI: -12.6; 35.3). As compared to morphologically selected embryos, performance of PGT-A did not increase the risk of small for gestation age (SGA) (3.9% vs. 4.1%, OR: 1.13; 95% CI: 0.86-1.50), low birth weight (LBW) (<2500 g but ≥1500 g) (5.8% vs. 5.5%, OR: 0.90; 95% CI: 0.66-1.21), or very low birthweight (<1500 g) (1.3% vs. 1.0%, OR: 0.44; 95% CI: 0.44 (0.18-1.10). There was no increased risk of preterm birth (PTB) associated with pregnancy resulting from PGT-A embryos vs. non PGT-A embryos (15.8% vs. 16.4%, OR: 0.94; 95% CI: 0.81-1.09). CONCLUSIONS: In our study, trophectoderm biopsy for PGT-A did not increase the risk of SGA, LBW or PTB in IVF pregnancies.

Live birth associated with peak serum estradiol levels in letrozole intrauterine insemination cycles.

OBJECTIVE: To identify whether the serum estradiol (E2) level on the day of human chorionic gonadotropin (hCG) trigger or luteinizing hormone (LH) surge (hCG-LH) was associated with the live birth rate (LBR) during ovulation induction (OI) or controlled ovarian hyperstimulation with letrozole followed by intrauterine insemination (IUI). DESIGN: Retrospective cohort study. SETTING: Large, multicenter private practice. PATIENT(S): A total of 2,368 OI-IUI cycles in patients treated with letrozole followed by IUI were evaluated from January 1, 2014, to July 31, 2019. INTERVENTION(S): Ovulation induction with letrozole, followed by autologous IUI. MAIN OUTCOME MEASURE(S): The primary outcome measure was the LBR as a function of the serum E2 level at the time of hCG administration or LH surge, adjusting for age, body mass index, the largest follicle diameter, and the number of follicles ≥14 mm in diameter. The clinical pregnancy rate as a function of the E2 level, pregnancy rate as a function of the lead follicle diameter, and pregnancy loss rates were the secondary outcome variables. RESULT(S): A total of 2,368 cycles met the inclusion criteria. Outcomes were evaluated at the 25th (E2 level, 110 pg/mL), 50th (157 pg/mL), 75th (225 pg/mL), and 90th (319 pg/mL) percentiles. The LBRs ranged from 9.4% to 11.1% in the lower E2 cohorts and from 12.5% to 13.5% in the higher E2 cohorts. The LBR was significantly greater in the cohort of women with higher E2 levels in all percentile comparisons except for the 90th percentile. The mean periovulatory follicle diameter of ≥20 or <20 mm was not independently associated with the LBR or clinical pregnancy rate, despite a significantly higher mean E2 level in the larger follicle group. CONCLUSION(S): In letrozole OI cycles followed by IUI, lower LBRs and clinical pregnancy rates were found in women with lower E2 levels than in those with higher E2 levels at the 25th, 50th, and 75th percentile E2 level quartiles. Where possible, delaying hCG trigger until the E2 level increases after aromatase inhibition and approaches the physiologic periovulatory level may improve the pregnancy rates with letrozole followed by IUI.

Live birth per embryo transfer with next generation sequencing preimplantation genetic testing: an analysis of 26,107 cycles.

The technique and platform used for preimplantation genetic testing for aneuploidy (PGT-A) have undergone significant changes over time. The contemporary technique utilizes trophectoderm biopsy followed by next-generation sequencing (NGS). The goal of this study was to explore the role of PGT-A using NGS technique exclusively in contemporary in vitro fertilization (IVF) practice. For this, we performed a retrospective analysis of a large dataset collected from the Shady Grove Fertility (SGF) multicentre practice. All autologous IVF cycles which were followed by at least one single embryo transfer (ET) (fresh and/or frozen) between January 2017 to July 2020, were included. Our study group included patients who had PGT-A and the control group included patients who did not proceed with PGT-A. The primary outcome was the live birth rate (LBR) per transfer. All age-adjusted LBR was higher in the PGT-A group than the non-PGT-A group (48.9% vs. 42.7%, p < 0.001), except in women <35 years old among single embryo frozen ETs. Similarly, LBR in the PGT-A group was higher in all ages except in women <35 years old (48.7% vs. 41.7%, p < 0.001) when all single embryos fresh and frozen ETs were included. In patients of decreased ovarian reserve, transfer of euploid embryo was associated with higher LBR (46.7% vs. 26.7%, p < 0.001) whereas miscarriages were lower in patients with unexplained infertility (9.3% vs. 11.3%, p = 0.007 and endometriosis (8.9% vs. 11.6%, p < 0.001) following euploid embryo transfer. To conclude, the transfer of euploid embryos tested via NGS PGT-A was associated with improved LBR per transfer in women ≥35 years old.

Meeting the demand for fertility services: the present and future of reproductive endocrinology and infertility in the United States.

The field of reproductive endocrinology and infertility (REI) is at a crossroads; there is a mismatch between demand for reproductive endocrinology, infertility and assisted reproductive technology (ART) services, and availability of care. This document's focus is to provide data justifying the critical need for increased provision of fertility services in the United States now and into the future, offer approaches to rectify the developing physician shortage problem, and suggest a framework for the discussion on how to meet that increase in demand. The Society of REI recommend the following: 1. Our field should aggressively explore and implement courses of action to increase the number of qualified, highly trained REI physicians trained annually. We recommend efforts to increase the number of REI fellowships and the size complement of existing fellowships be prioritized where possible. These courses of action include: a. Increase the number of REI fellowship training programs. b. Increase the number of fellows trained at current REI fellowship programs. c. The pros and cons of a 2-year focused clinical fellowship track for fellows interested primarily in ART practice were extensively explored. We do not recommend shortening the REI fellowship to 2 years at this time, because efforts should be focused on increasing the number of fellowship training slots (1a and b). 2. It is recommended that the field aggressively implements courses of action to increase the number of and appropriate usage of non-REI providers to increase clinical efficiency under appropriate board-certified REI physician supervision. 3. Automating processes through technologic improvements can free providers at all levels to practice at the top of their license.

Comparative analysis of different laparoscopic hysterectomy procedures.

PURPOSE: To compare the antecedent gynecological characteristics, indications for, and complications associated with, the different laparoscopic approaches to hysterectomy, in women with benign gynecological conditions. METHODS: A retrospective cohort study of 957 patients who underwent laparoscopic supracervical (LSH), total (TLH), and assisted vaginal (LAVH) hysterectomies between January 2003 and December 2009. RESULTS: Among 957 LH, 799 (83.5%) were LSH, 62 (6.4%) TLH, and 96 (10.1%) LAVH. Demographic characteristics were not different among the groups. Antecedent gynecologic conditions that were associated with the type of laparoscopic hysterectomy (LH) performed were: postmenopausal bleeding [LAVH vs. LSH, odds ratio (OR) 2.20; 95% confidence interval (CI) 1.04-4.65], previous pelvic surgery (TLH vs. LSH, OR 1.92; CI 1.05-3.52), previous cesarean delivery (LAVH vs. LSH, OR 0.39; CI 0.21-0.76), and prior hysteroscopy (LAVH vs. LSH, OR 0.29; CI 0.16-0.50). Preoperative diagnoses that were associated with the choice of LH were: menometrorrhagia (LAVH vs. LSH, OR 0.23; CI 0.14-0.38; TLH vs. LSH, OR 0.50; CI 0.26-0.98), uterine fibroids (LAVH vs. LSH, OR 0.25; CI 0.15-0.41), endometrial hyperplasia (TLH vs. LSH, OR 5.5; CI 2.04-14.84), and cervical dysplasia (TLH vs. LSH, OR 17.1; CI 6.83-42.79; LAVH vs. LSH, OR 8.05; CI 3.05-22.06). Estimated blood loss, operating time, and length of hospital stay were significantly reduced with LSH. CONCLUSION: Antecedent gynecological history and the indications for surgery were associated with the type of LH performed in our institution. LSH was the most common approach and was associated with significantly less morbidity.

Oocyte Retrieval in Asymptomatic Patients Positive for SARS-CoV-2.

Objective: To report two cases of oocyte retrieval performed in asymptomatic SARS-CoV-2-positive patients. Design: Case report. Setting. Outpatient private practice infertility center. Patients. A 28-year-old woman at risk for OHSS who took her trigger injection prior to testing positive for SARS-CoV-2 and a 19-year-old oncofertility patient who tested positive prior to retrieval due to a family exposure. Both patients were asymptomatic. Main Outcome Measures. Cycle outcomes, patient safety, and staff safety. Results: Both patients underwent successful oocyte retrieval procedures without developing symptoms or complications from COVID-19. No staff members that cared for these patients developed symptoms of COVID-19. Conclusion: Worsening fertility outcomes and potential for psychological and financial burdens to the patient must be balanced with risk of perioperative complications in patients testing positive for SARS-CoV-2. As we continue to provide fertility care in a world with COVID-19, appropriate risk mitigation strategies should be implemented to minimize exposure to SARS-CoV-2.

FKBP51 Contributes to Uterine Leiomyoma Pathogenesis by Inducing Cell Proliferation and Extracellular Matrix Deposition.

The FK506-binding protein 51 (FKBP51) binds progesterone receptor (PR), glucocorticoid receptor (GR), and androgen receptor (AR) to coregulate their transcriptional activity. We evaluated FKBP51 expression and function in human leiomyoma vs. myometrial tissues and primary cultures to discover FKBP51 role(s) in the pathogenesis of leiomyomas. Quantification of in situ FKBP51 mRNA and protein levels inpaired myometrial vs. leiomyoma tissues from proliferative and secretory phases were analyzed by qPCR (n = 14), immunoblotting (n = 20), and immunohistochemistry (n = 12). Control (scramble) vs. FKBP5 siRNA-transfected leiomyoma cell cultures were assessed for proliferation, apoptosis, and mRNA levels of genes involved in cell survival and extracellular matrix (ECM) formation. Significantly higher FKBP5 mRNA levels were detected in leiomyoma vs. paired myometrium (P < 0.001). Immunoblot (P = 0.001) and immunostaining (P ≤ 0.001) confirmed increased FKBP51 levels in leiomyoma vs. paired myometrium. Compared to control siRNA transfection, FKBP5-silenced leiomyoma cell cultures displayed significantly decreased cell survival factors and reduced proliferation (P < 0.05). Moreover, qPCR analysis revealed significantly lower mRNA levels of ECM, TIPM1, and TIPM3 proteins in FKBP5-silenced leiomyoma cell cultures (P < 0.05). Increased FKBP51 expression in leiomyoma likely involves dysregulation of steroid signaling by blocking GR and PR action and promoting proliferation and ECM production. Evaluating the effect of FKBP51 inhibition in preclinical studies will clarify its significance as a potential therapeutic approach against leiomyoma.

Reduction of Heavy Menstrual Bleeding in Women Not Designated as Responders to Elagolix Plus Add Back Therapy for Uterine Fibroids.

Objective: To assess outcomes of women with uterine fibroids (UFs) and heavy menstrual bleeding (HMB) treated with 300 mg elagolix twice daily plus add-back therapy (E2 1 mg/NETA 0.5 mg once daily) or placebo who were not considered responders in pooled analysis of two phase 3, 6-month randomized clinical trials (Elaris UF-1 and UF-2). Methods: Responders were defined as women who met both primary end point bleeding criteria (<80 mL menstrual blood loss [MBL] during the final month and ≥50% reduction in MBL from baseline to the final month) and either completed the study or discontinued due to predefined reasons. Thus, women termed nonresponders who were analyzed in this study who met neither or one bleeding end point or met both criteria but prematurely discontinued treatment because of adverse events, perceived lack of efficacy, or required surgical or interventional treatment for UFs were analyzed in this study. This post hoc analysis assessed mean changes from baseline in MBL, as well as adverse events. Results: Among 367 women receiving elagolix with add-back with observed data, 89 (24%) were not considered responders. Within this subset, 17 (19%) women met both bleeding criteria but prematurely discontinued treatment for the reasons mentioned above, while 23 (26%) met one bleeding criterion and 49 (55%) met neither bleeding criteria, regardless of discontinuation status. Among all nonresponders, a numerical trend toward greater mean reductions in MBL was observed in those receiving elagolix with add-back, compared with placebo group nonresponders. No differences in adverse events were observed between responders and nonresponders. Conclusion: Forty of 89 (45%) women with HMB and UFs who were classified as nonresponders in the UF-1 or UF-2 trials may have had a clinically meaningful response to elagolix with add-back therapy because they met at least one of the objective bleeding criteria. Clinical Trial Registration: Clinicaltrials.gov, NCT02654054 and NCT02691494. (NEJM 2020; 382:328-340) DOI: 10.1056/NEJMoa1904351.