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Background: Endometrial cavity fluid (ECF) is occasionally observed during assisted reproductive technology (ART) cycles. However, few reports have described its prevalence or significance.Methods and Results: We examined the relationships between ECF, clinical pregnancy rate (CPR), tubal factor infertility and ultrasound-visible (USV) hydrosalpinges. In 843 ART cycles involving 721 patients, ECF was observed during stimulation in 57 cycles and after human chorionic gonadotrophin (HCG) administration in 12 cycles, with an overall incidence of 8.2% (69/843). When ECF was observed during stimulation, the cancellation rate due to poor ovarian response was significantly higher (29.8 versus 16.9%, P <0.05) and the CPR per started cycle was significantly lower (26.3 versus 42.4%, P <0.05) than cycles without ECF. When ECF developed after HCG administration, the CPR was similar compared with that of the group for which ECF was not observed. In the 327 cycles involving tubal factor infertility patients, USV hydrosalpinges were noted in 71 cycles (71/327; 21.7%), and ECF developed in five of those cycles (5/71; 7.0%). A total of 27 cycles during which ECF developed (27/57, 47.4%) involved non-tubal factor patients.Conclusions: ECF during stimulation was associated with increased cancellation rates and lower CPRs per started cycle, and was not associated with USV hydrosalpinges. Furthermore, ECF observed after HCG administration did not impact CPR and may represent a different clinical entity. [ABSTRACT FROM AUTHOR]

Background: Embryo transfer represents one of the most critical procedures in the practice of assisted reproduction. The objective of this study was to identify retrospectively the minimum number of embryo transfers required to train providers properly in this skill.Methods and Results: The study group consisted of 204 patients who received embryo transfers between January 1996 and March 2000 in a university-based programme of assisted reproduction. The main outcome measure was clinical pregnancies per embryo transfer. Five Fellow trainees performed a total of 204 embryo transfers for an overall pregnancy rate of 45.5% per embryo transfer (93/204). In comparison, the programme pregnancy rate per transfer for experienced providers was 47.3% (560/1179). A chronological graph of each individual trainee's experience for the first 50 embryo transfers performed suggested a lower initial pregnancy rate for three of the five trainees. To determine whether a learning curve might exist, results of the first 25 transfers were compared as a subgroup with the second 25 transfers. Pregnancy rates were lower for the 1-25 transfer subgroup than in the 26-50 subgroup for three of the five Fellow trainees, although the difference was not statistically significant.Conclusion: Clinical pregnancy rates of Fellows-in-training were indistinguishable statistically from those of experienced staff by 50 transfers. [ABSTRACT FROM AUTHOR]

Human embryos are selected for transfer using morphology at the cleaving and blastocyst stages. Zygote morphology has been related to implantation and pregnancy. The aim of this study was to relate pronuclear morphology to blastocyst development. Zygotes were scored according to distribution and size of nucleoli within each nucleus. Zygotes displaying equality between the nuclei had 49.5% blastocyst formation and those with unequal sizes, numbers or distribution of nucleoli had 28% blastocyst formation. Cleaving embryos that were selected initially by zygote morphology and secondarily by morphology on day 3 had increased implantation (IR) and pregnancy rates (PR; 31 and 57%), compared with those selected by morphology alone (19 and 33% respectively; P: < 0.01). There was a significant difference between zygote-scored and non-scored cycles on day 3 (PR: 57 versus 33%; IR: 31 versus 19%) and on day 5 (PR: 73 versus 58%; IR; 52 versus 39%). Zygote scoring can maintain pregnancy rates for both day 3 and day 5 transfers, increase implantation rates and reduce the numbers of embryos required to achieve a pregnancy. [ABSTRACT FROM AUTHOR]

Objective: To explore the cycle characteristics and outcomes of single and coupled intended fathers (SCIFs) using assisted reproductive technology., Design: Cross-sectional study., Setting: Multicenter, fertility practices from 2016 to 2020., Patients: In this study, cycles among SCIFs with access to fertility coverage from 2016 to 2020 were included., Interventions: None., Main Outcome Measures: Our primary outcome was live birth rate. The secondary outcomes included the number of embryos transferred, miscarriage rate, and incidence of multifetal birth., Results: Five single and 39 coupled intended fathers completed an in vitro fertilization cycle with a majority using egg donation and an agency-based gestational carrier (69.7%, 83/119). In most couples, both partners wanted to serve as the sperm source (64.4%, 29/45). The vast majority (97.7%, 43/44) also used preimplantation genetic testing for aneuploidy. Among the embryo transfer (ET) cycles (n = 27), most consisted of a single euploid ET (74.07%, 20/27), whereas the remaining consisted of a double euploid ET (25.92%, 7/27). The SCIFs had high rates of success, with a live birth rate of 85.19% (23/27). A mean of 1.26 ± 0.44 embryos were transferred, with a majority resulting in singleton birth (70.37%, 19/27)., Conclusions: Our study of SCIFs using assisted reproductive technology in the United States demonstrates that this population shares similar preferences for sperm source and the use of preimplantation genetic testing. Clinical outcomes suggest that this population is successful at achieving a live birth when using egg donation and a gestational carrier., (© 2022 The Author(s).)

Background: Previous evidence indicates associations between the female reproductive tract microbiome composition and reproductive outcome in infertile patients undergoing assisted reproduction. We aimed to determine whether the endometrial microbiota composition is associated with reproductive outcomes of live birth, biochemical pregnancy, clinical miscarriage or no pregnancy., Methods: Here, we present a multicentre prospective observational study using 16S rRNA gene sequencing to analyse endometrial fluid and biopsy samples before embryo transfer in a cohort of 342 infertile patients asymptomatic for infection undergoing assisted reproductive treatments., Results: A dysbiotic endometrial microbiota profile composed of Atopobium, Bifidobacterium, Chryseobacterium, Gardnerella, Haemophilus, Klebsiella, Neisseria, Staphylococcus and Streptococcus was associated with unsuccessful outcomes. In contrast, Lactobacillus was consistently enriched in patients with live birth outcomes., Conclusions: Our findings indicate that endometrial microbiota composition before embryo transfer is a useful biomarker to predict reproductive outcome, offering an opportunity to further improve diagnosis and treatment strategies. Video Abstract., (© 2021. The Author(s).)

Research Questions: Can a previously defined relationship between sperm capacitation and the probability of a man generating pregnancy within three cycles, prospectively predict male fertility in diverse clinical settings? A second study asked, what is the prevalence of impaired sperm fertilizing ability in men questioning their fertility (MQF), and does this relate to traditional semen analysis metrics?, Design: In the multicentric, prospective observational study, data (n = 128; six clinics) were analysed to test a published relationship between the percentage of fertilization-competent, capacitated spermatozoa (Cap-Score) and probability of generating pregnancy (PGP) within three cycles of intrauterine insemination. Logistic regression of total pregnancy outcomes (n = 252) assessed fit. In the cohort comparison, Cap-Scores of MQF (n = 2155; 22 clinics) were compared with those of 76 fertile men., Results: New outcomes (n = 128) were rank-ordered by Cap-Score and divided into quintiles (25-26 per group); chi-squared testing revealed no difference between predicted and observed pregnancies (P = 0.809). Total outcomes (n = 252; 128 new + 124 previous) were pooled and the model recalculated, yielding an improved fit (P < 0.001). Applying the Akaike information criterion found that the optimal model used Cap-Score alone. Cap-Scores were performed on 2155 men (with semen analysis data available for 1948). To compare fertilizing ability, men were binned by PGP (≤19%, 20-29%, 30-39%, 40-49%, 50-59%, ≥60%). Distributions of PGP and the corresponding Cap-Scores were significantly lower in MQF versus fertile men (P < 0.001). Notably, 64% of MQF with normal volume, concentration and motility (757/1183) had PGP of 39% or less (Cap-Scores ≤31), versus 25% of fertile men., Conclusions: Sperm capacitation prospectively predicted male fertility. Impaired capacitation affects many MQF with normal semen analysis results, informing diagnosis versus idiopathic infertility., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Preimplantation genetic testing (PGT) has been successfully applied to reduce the risk of miscarriage, improve IVF success rates, and prevent inheritance of monogenic disease and unbalanced translocations. The present study provides the first method capable of simultaneous testing of aneuploidy (PGT-A), structural rearrangements (PGT-SR), and monogenic (PGT-M) disorders using a single platform. Using positive controls to establish performance characteristics, accuracies of 97 to >99% for each type of testing were observed. In addition, this study expands PGT to include predicting the risk of polygenic disorders (PGT-P) for the first time. Performance was established for two common diseases, hypothyroidism and type 1 diabetes, based upon availability of positive control samples from commercially available repositories. Data from the UK Biobank, eMERGE, and T1DBASE were used to establish and validate SNP-based predictors of each disease (7,311 SNPs for hypothyroidism and 82 for type 1 diabetes). Area under the curve of disease status prediction from genotypes alone were 0.71 for hypothyroidism and 0.68 for type 1 diabetes. The availability of expanded PGT to evaluate the risk of polygenic disorders in the preimplantation embryo has the potential to lower the prevalence of common genetic disease in humans., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: To evaluate whether persistence of pelvic pain after excision of endometriosis was associated with adenomyosis as defined by a thickened uterine junctional zone (JZ) on magnetic resonance (MR) imaging., Design: Prospective clinical trial., Setting: Government research hospital., Patient(s): Fifty-three women with chronic pelvic pain., Intervention(s): Preoperative MR imaging to measure uterine JZ thickness, surgical excision, and pathologic diagnosis of endometriosis. Those with biopsy-proven endometriosis were randomized to raloxifene or placebo. Visual analog scale (VAS) was used to rate dysmenorrhea and nonmenstrual pain severity before surgery and 3 months later., Main Outcome Measure(s): Comparison of JZ thickness and pain severity before and 3 months after surgery in women with endometriosis controlling for medical treatment., Result(s): Forty of the 53 patients had biopsy-proven endometriosis, and 6 of these 40 women with endometriosis had a thickened JZ. Overall, dysmenorrhea at 3 months was positively correlated with preoperative JZ thickness (r = 0.47, P=.01). Dysmenorrhea pain severity showed no significant decrease in those patients whose JZ measured >or=11 mm compared with those with JZ <8 mm (P<.0001; VAS decreased 4.3 +/- 0.6), or >or=8 and <11 mm (P<.02; VAS decreased 4.8 +/- 1.3). Nonmenstrual pain severity was correlated with JZ thickness (r = 0.51, P=.004) at 3 months with a significant decrease in nonmenstrual pain only in women with a JZ <8 mm (VAS decreased 4.0 +/- 0.7, P<.0001). The association between dysmenorrhea and nonmenstrual pain reduction and thinner JZ remained after controlling for medical treatment., Conclusion(s): Following surgical excision of endometriosis, chronic pelvic pain was significantly more likely to persist with JZ thickness >11mm on preoperative MR imaging. This suggests that myometrial JZ abnormalities or adenomyosis may contribute to chronic pelvic pain in women with endometriosis.

Objective: Our purpose was to compare outcomes of women with triplet gestations conceived via assisted reproductive technology who chose expectant management or multifetal pregnancy reduction., Study Design: We performed a retrospective review of all women who initiated assisted reproductive technology cycles from August 1995 through July 1997 with ultrasonographic documentation of triplets exhibiting fetal heart tones at 9 weeks of gestation (N = 127). Patients were then uniformly referred to a maternal-fetal medicine specialist and to 3 centers offering multifetal pregnancy reduction., Results: Thirty-six percent of patients (46/127) chose multifetal pregnancy reduction with 95% undergoing reduction to twins. In the expectant management group, 13.6% of pregnancies were reduced spontaneously after 9 weeks of gestation. The "take home" infant per delivery rates for the multifetal pregnancy reduction and expectant management groups were 87% and 90.1%, respectively (P =.66). The mean gestational ages at delivery (+/-SE) for the multifetal pregnancy reduction and expectant management groups were 33.25 +/- 1. 03 weeks and 32.04 +/- 0.58 weeks (P =.23), and the mean birth weights of infants delivered at >24 weeks of gestation were 2226 +/- 79 and 1796 +/- 44, respectively (P <.0001). There were no significant differences in perinatal mortality, gestational age at delivery, or "take home" infant per delivery rates between these groups., Conclusions: These data suggest that multifetal pregnancy reduction does not have a significant impact on the probability of live birth or on gestational age at delivery for women with triplets conceived with assisted reproductive technology.

Purpose: To examine the effect of intracytoplasmic sperm injection (ICSI) on embryo fragmentation and implantation rates in those embryos chosen for transfer compared to conventional in vitro fertilization (IVF)., Methods: We compared 253 infertility patients (71 ICSI and 182 IVF) with respect to age, semen analysis, number of embryos transferred, embryo fragmentation, implantation rate, and pregnancy rate. Embryo fragmentation was determined by one observer at the same laboratory over the entire study period., Results: A statistically significant difference was observed in mean embryo grade between IVF (2.2 +/- 0.84) and ICSI (2.5 +/- 0.77), P = 0.01. Additionally, the IVF patients had significantly more nonfragmented (grade I) embryos compared to the ICSI group, P < 0.01., Conclusions: These data suggest that ICSI, irrespective of semen parameters, may increase embryo fragmentation and produce fewer nonfragmented grade I embryos while maintaining implantation and pregnancy rates similar to conventional IVF.

Objective: To compare an ovarian stimulation protocol using microdose follicular phase GnRH agonist (GnRH-a) and oral contraceptive (OC) pills to a luteal phase GnRH-a protocol., Design: Retrospective analysis., Setting: University affiliated IVF program., Patient(s): One hundred seventy patients who underwent IVF and ET in 1996., Intervention(s): Patients were assigned to either a midluteal start of leuprolide acetate (LA) 1 mg/d, reduced to 0.5 mg/d after addition of gonadotropins (LUT), or OC pills until cycle day 0 followed by 20 microg of LA every 12 hours on cycle day 3 with addition of gonadotropins on cycle day 5 (MICRO)., Main Outcome Measure(s): Number of FSH ampules, days of stimulation, peak E2, and number of oocytes retrieved., Result(s): There were no statistically significant differences in the main outcome measures between the two groups using an age-matched ANOVA. Clinical pregnancy rate per cycle start was not statistically different (LUT = 54%, and MICRO = 37%). The cancellation rate was significantly higher in the MICRO group (22.5% vs. 8.2%)., Conclusion(s): Given the higher cancellation rate in the microdose group, a randomized clinical trial is required to determine the possible benefit of a lower dose of GnRH-a in patients with normal ovarian function.

The 5'-untranslated region of the human prolactin receptor (hPRLR) gene contains two alternative first exons, hE1(3), the human counterpart of the rat and mouse E1(3) and a novel human type of alternative first exon termed hE1N, also a common non-coding exon 2 and a third exon containing the translation initiation codon. hE1(3) was localized approximately 800 bp 5' from the hE1N in the genome. The two distinct first exons hE1(3) and hE1N are expressed in human breast tissue, breast cancer cells, gonads and liver. Overall, the transcript containing hE1(3) is prevalent in most tissues. The coding region of the gene comprises eight exons (exon 3-10), in which exon 10 encodes most of the intracellular domain. hE1(3) and hE1N are transcribed from alternative promoters hPIII and hP(N), respectively. The hPIII, containing identical Sp1 and C/EBP elements as in the rodent promoters, shares 81% similarity in the region -480/-106 to both the rat and mouse. The novel promoter hP(N) contains putative binding sites for ETS-family proteins and a half-site for nuclear receptors. Therefore, both promoters likely utilize distinct mechanisms in controlling the hPRLR gene transcription. The different promoter utilization of the hPRLR gene in diverse tissues may confer differential prolactin response through activation of different promoters.

Objective: Our purpose was to evaluate the efficacy of cyclosporine in preventing primary postsurgical adhesions in the rat model., Study Design: Thirty-two Sprague-Dawley rats underwent unilateral uterine horn injury with a combination of unipolar and bipolar cautery. Sixteen of the rats were randomized to the treatment group and received preoperative and daily cyclosporine dosing (10 mg/kg) by gavage for 14 days. At the end of the study all animals were killed, and a standard adhesion scoring system was applied by a blinded examiner., Results: Adhesions were present in 75% of rats in both groups. Treatment did not affect the total adhesion score., Conclusion: Cyclosporine does not appear promising as a means to decrease postsurgical adhesion formation.