Male infertility.

It is estimated that infertility affects 8-12% of couples globally, with a male factor being a primary or contributing cause in approximately 50% of couples. Causes of male subfertility vary highly, but can be related to congenital, acquired, or idiopathic factors that impair spermatogenesis. Many health conditions can affect male fertility, which underscores the need for a thorough evaluation of patients to identify treatable or reversible lifestyle factors or medical conditions. Although semen analysis remains the cornerstone for evaluating male infertility, advanced diagnostic tests to investigate sperm quality and function have been developed to improve diagnosis and management. The use of assisted reproductive techniques has also substantially improved the ability of couples with infertility to have biological children. This Seminar aims to provide a comprehensive overview of the assessment and management of men with infertility, along with current controversies and future endeavours.

Biosimilar recombinant follitropin alfa preparations versus the reference product (Gonal-F®) in couples undergoing assisted reproductive technology treatment: a systematic review and meta-analysis.

BACKGROUND: Live birth has increasingly been identified as the standard clinical approach to measure the success of medically assisted reproduction (MAR). However, previous analyses comparing biosimilar preparations of follitropin alfa versus the reference product (GONAL-f®, Merck KGaA, Darmstadt, Germany or GONAL-f® RFF; EMD Serono, Inc., Rockland, MA), have had insufficient power to detect differences in clinically meaningful outcomes such as live birth. METHODS: Medline, Embase, the Cochrane Library, Web of Science and clinical trial registries were searched for randomised controlled trials (RCTs) and conference abstracts comparing biosimilar follitropin alfa versus the reference product in controlled ovarian stimulation (COS) cycles published before 31 October 2020. Only studies in humans and publications in English were included. Retrieved studies were screened independently by two authors based on titles and abstracts, and then by full text. INCLUSION CRITERIA: RCTs comparing follitropin alfa biosimilar preparations with the reference product in infertile patients of any age, with any type of infertility for any duration, undergoing COS for the purposes of MAR treatment (including frozen cycles). The primary outcome was live birth. Combined data for biosimilar preparations were analysed using a fixed-effects model. RESULTS: From 292 unique records identified, 17 studies were included in the systematic review, representing five unique RCTs that were included in the meta-analysis. Rates of live birth (RR = 0.83, 95% CI 0.71, 0.97; 4 RCTs, n = 1881, I2 = 0%), clinical pregnancy (RR = 0.82, 95% CI 0.72, 0.94; 4 RCTs, n = 2222, I2 = 0%) and ongoing pregnancy (RR = 0.81, 95% CI 0.68, 0.96; 4 RCTs, n = 1232, I2 = 0%) were significantly lower with biosimilar preparations versus the reference product. Rates of cumulative live birth and cumulative clinical pregnancy were also significantly lower with biosimilars versus the reference product. There was high risk of publication bias. CONCLUSIONS: This meta-analysis included data from RCTs evaluating the efficacy and safety of the biosimilar follitropin alfa preparations and demonstrated lower probability of live birth and pregnancy (ongoing and clinical) in couples treated with biosimilar preparations compared with the reference product. This study provides more insight into the differences between biosimilar r-hFSH preparations and the reference product than previously reported. TRIAL REGISTRATION: Registration number: CRD42019121992 .

Impacts of Cyclosporin A on clinical pregnancy outcomes of patients with a history of unexplained transfer failure: a retrospective cohort study.

BACKGROUND: A rapid development in assisted reproductive technology (ART) has led to a surge in its popularity among target couples. However, elucidation on the molecular mechanism and effective solutions for a common problem posed by ART, namely transfer failure, is still lacking. The new therapeutic potential of cyclosporin A (CsA), a typical immunosuppressant widely used in the treatment of rejection after organ transplantation, in recurrent pregnancy loss (RPL) patients may inspire some novel transfer failure therapies in the future. To further explore the clinical effects of CsA, this study investigated whether its application can improve clinical pregnancy outcomes in patients with a history of unexplained transfer failure in frozen-thawed embryo transfer (FET) cycles. METHODS: Data from a retrospective cohort investigation (178 frozen-thawed embryo transfer cycles in 178 patients) were analysed using binary logistic regression to explore the relationship between CsA treatment and clinical pregnancy outcomes; the odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated as a measure of relevancy. Implantation rate was the main outcome measure. RESULTS: There was no difference in the fine adjusted OR (95 % CI) of the implantation rate [1.251 (0.739-2.120)], clinical pregnancy rate [1.634 (0.772-3.458)], chemical pregnancy rate [1.402 (0.285-6.909)], take-home baby rate [0.872 (0.423-1.798)], multiple births rate [0.840 (0.197-3.590)], preterm birth [1.668 (0.377-7.373)], abnormal birth weight [1.834 (0.533-6.307)] or sex ratio [0.956 (0.339-2.698)] between the CsA-treated group and control group. No birth defects were observed in the present study. CONCLUSIONS: Although CsA does not affect infant characteristics, it has no beneficial effects on the clinical pregnancy outcomes in patients with a history of unexplained transfer failure in FET cycles.

Trends and factors related to adolescent pregnancies: an incidence trend and conditional inference trees analysis of northern Nicaragua demographic surveillance data.

BACKGROUND: We aimed to identify the 2001-2013 incidence trend, and characteristics associated with adolescent pregnancies reported by 20-24-year-old women. METHODS: A retrospective analysis of the Cuatro Santos Northern Nicaragua Health and Demographic Surveillance 2004-2014 data on women aged 15-19 and 20-24. To calculate adolescent birth and pregnancy rates, we used the first live birth at ages 10-14 and 15-19 years reported by women aged 15-19 and 20-24 years, respectively, along with estimates of annual incidence rates reported by women aged 20-24 years. We conducted conditional inference tree analyses using 52 variables to identify characteristics associated with adolescent pregnancies. RESULTS: The number of first live births reported by women aged 20-24 years was 361 during the study period. Adolescent pregnancies and live births decreased from 2004 to 2009 and thereafter increased up to 2014. The adolescent pregnancy incidence (persons-years) trend dropped from 2001 (75.1 per 1000) to 2007 (27.2 per 1000), followed by a steep upward trend from 2007 to 2008 (19.1 per 1000) that increased in 2013 (26.5 per 1000). Associated factors with adolescent pregnancy were living in low-education households, where most adults in the household were working, and high proportion of adolescent pregnancies in the local community. Wealth was not linked to teenage pregnancies. CONCLUSIONS: Interventions to prevent adolescent pregnancy are imperative and must bear into account the context that influences the culture of early motherhood and lead to socioeconomic and health gains in resource-poor settings.

Does quantity equal quality?-A morphokinetic assessment of embryos obtained from young women with decreased ovarian response to controlled ovarian stimulation.

PURPOSE: To assess oocyte quality in young patients with decreased ovarian response to controlled ovarian stimulation using time-lapse analysis. METHODS: A retrospective cohort study conducted at five medical centers between 2013 and 2017. The "decreased ovarian response" (DOR) group consisted of 241 women who underwent controlled ovarian stimulation with ≤ 5 retrieved oocytes and 519 cultured embryos. The "normal response" (NOR) group consisted of 667 women with ≥ 6 retrieved oocytes resulting in 3633 embryos. Data included annotation of morphokinetic events of embryos cultured in a time-lapse incubator from time of pronuclei appearance to time of starting blastocyst formation (tSB). Comparison was made between morphokinetic parameters of DOR and NOR patients with additional subgroup analysis according to the implantation status. RESULTS: Implantation and clinical pregnancy rates were significantly higher in the NOR group compared with the DOR group (44.5% vs. 31.6% and 51.5% vs. 37.7%, respectively; p < 0.05). Embryos from the DOR group reached the morphokinetic milestones later than embryos obtained from NOR patients. In the DOR group, implanted embryos reached starting blastocyst formation (tSB) faster than embryos which failed to be implanted, however, manifested a protracted course compared with implanted embryos from the NOR group. In a multivariate analysis-decreased ovarian response, nulliparity, number of transferred embryos, and t4, and were predictive for implantation. CONCLUSIONS: The quantitative decrease in ovarian response is associated with reduced oocyte quality, reflected by a slower developmental rate and lower implantation and pregnancy rates.

A novel embryo quality scoring system to compare groups of embryos at different developmental stages.

PURPOSE: To construct a new embryonic quality scoring system to compare groups of embryos at different developmental stages. METHODS: Based on a hypothesis that the implantation potential of any embryo in an ovum pickup (OPU) cycle remains the same at any stage of development, be it day 2, 3, or 5, a new embryo quality scoring (EQS) system was designed. It was based on the analysis of the clinical results of 1610 single embryo transfers. We validated this scoring system in the comparison of embryonic quality between groups by evaluating the mean scores calculated at day 2, day 3, and day 5 for 957 embryos (150 cycles) from 3 different groups. We then compared EQSs of patients with pregnancy favorable factors (group A) such as young age and high AMH levels, with the patients with contra features (group B). RESULTS: We confirmed that each mean EQS assessed at different stages of embryonic development within the same group was similar. The mean EQSs on day 3 and day 5 in group A were significantly higher than the mean EQSs on days 2, 3, and 5 in group B. CONCLUSION: The novel EQS system proposed by us enables embryonic quality comparison between groups of embryos at different developmental stages.

Changes in thyroid function during controlled ovarian hyperstimulation (COH) and its impact on assisted reproduction technology (ART) outcomes: a systematic review and meta-analysis.

BACKGROUND: To investigate the thyroid function changes during controlled ovarian hyperstimulation (COH) and ascertain its impact on reproductive outcomes. METHODS: We conducted meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was performed to identify studies reported changes in thyroid parameters during COH. We analyzed thyroid-stimulating hormone (TSH) levels, free thyroxin (fT4) levels, changes in estrogens (E2), thyroxine-binding globulin (TBG), relative risks (RRs) of clinical pregnancy rate (CPR), live birth rate (LBR), and mean difference (MD) of TSH increment between the miscarriage group and ongoing pregnancy group. RESULTS: This meta-analysis included fifteen individual studies (n = 1665 subjects). At the end of COH, the mean TSH (2.53 mIU/L; 95% CI, 2.19 to 2.88; I2 = 92.9%) exceeded the upper limit (2.5 mIU/L) and remained above the threshold until one month following embryo transfer (ET). Thyroxin decreased from baseline to the end of COH (-0.18 ng/l; 95% CI, -0.35 to 0.00; I2 = 92.2%). The CPR and LBR of patients with TSH exceeding the cutoff after COH were significantly lower than those of patients with TSH below the threshold (CPR: RR, 0.62; 95% CI, 0.47 to 0.82; I2 = 0.0% and LBR: RR, 0.64; 95% CI, 0.44 to 0.92; I2 = 0.0%). The MD of the increment in TSH levels between the miscarriage and ongoing pregnancy groups was 0.40 mIU/L (95% CI, 0.15 to 0.65; I2 = 0.0%). CONCLUSIONS: This meta-analysis shows that TSH increases and fT4 decreases during COH. COH-induced thyroid disorder impairs reproductive outcomes.

Embryo quality, ploidy, and transfer outcomes in male versus female blastocysts.

PURPOSE: The goal is to determine if variations exist between male and female blastocysts in preimplantation measurements of quality and ploidy and in vitro fertilization elective single-embryo transfer (eSET) outcomes. METHODS: A retrospective chart review was conducted from a private fertility center's database of blastocysts undergoing preimplantation genetic testing for aneuploidy, along with details of eSET from this screened cohort. Main outcomes included preimplantation embryo quality and sex-specific eSET outcomes. RESULTS: A total of 3708 embryos from 578 women were evaluated, with 45.9% male and 54.1% female. The majority were High grade. No difference existed between embryo sex and overall morphological grade, inner cell mass or trophectoderm grade, or blastocyst transformation day. Female blastocysts had a higher aneuploidy rate than male blastocysts (P < 0.001). Five hundred thirty-nine eSETs from 392 women were evaluated, with High grade embryos more likely to have implantation (P < 0.001), clinical pregnancy (P < 0.001), and ongoing pregnancy (P = 0.018) than Mid or Low grade embryos. Day 5 blastocysts were more likely to have implantation (P = 0.018), clinical pregnancy (P = 0.005), and ongoing pregnancy (P = 0.018) than day 6 blastocysts. Male and female embryos had similar transfer outcomes, although female day 5 blastocysts were more likely to result in clinical pregnancy (P = 0.012), but not ongoing pregnancy, than female day 6 blastocysts. Male eSET outcomes did not differ by blastocyst transformation day. CONCLUSION: Male and female embryos have comparable grade and quality; however, female embryos were more likely to be aneuploid. Ongoing pregnancy rates did not differ by embryo sex. Day 5 embryos had more favorable transfer outcomes than day 6 embryos.

Effect of polymorphisms of MTHFR in controlled ovarian stimulation: a systematic review and meta-analysis.

OBJECTIVE: Although several studies have reported a potential impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on controlled ovarian stimulation (COS), the results remain controversial. The aim of the systematic review and meta-analysis was to evaluate the effect of MTHFR polymorphism on COS outcomes. METHODS: PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials databases were searched up to December 2, 2020. COS clinical outcomes based on gene polymorphisms were included. Two reviewers independently extracted the data. The primary outcome was the number of oocytes retrieved. The secondary outcomes were the number of metaphase II (MII) oocytes, stimulation duration, basal follicle-stimulating hormone (FSH) level, FSH dosage, positive pregnancy test, ongoing pregnancy rate, clinical pregnancy rate, miscarriage rate, and live birth rate. Meta-analysis was performed using a fixed-effect model or random-effect model with Review Man 5.3.5. Mean difference (MD) with 95% confidence intervals (95%CIs) was calculated for continuous outcomes. The quality assessment of included studies was evaluated by using the Newcastle-Ottawa Scale. RESULTS: Eleven studies were included in the systematic review, and seven studies with 2015 participants were included in the meta-analysis. Basal FSH level was significantly lower in CC homozygotes than TT homozygotes (four studies, 867 participants, MD - 0.54, 95%CI - 0.85 to - 0.23, P = 0.0006; I2 = 0%) of MTHFR (rs1801133). FSH dose was significantly fewer in CC homozygotes compared with CT heterogeneous (three studies, 949 participants, MD - 75.78, 95%CI - 135.23 to - 16.33, P = 0.01; I2 = 32%) or CT/TT model (three studies, 1097 participants, MD - 80.18, 95%CI - 135.54 to - 24.81, P = 0.005; I2 = 42%). Differences in the oocytes retrieved and stimulation duration were insignificant. Gene variants on MTHFR (rs1801133) and MTHFR (rs1801131) were reported in ongoing pregnancy rate, clinical pregnancy rate, and live birth rate. CONCLUSION: Studies to date indicate that polymorphisms of MTHFR could influence basal FSH level and FSH dose. The results could be useful to promote clinical practice on COS protocols. Further studies are needed to evaluate the clinical relevance of the multigene combination on COS.

The evolving landscape of donor egg treatment: success, women's choice, and anonymity.

PURPOSE: To analyze donor oocyte (DE) data across 6 years for oocyte usage efficiency, trends, and whether changes impacted outcomes. METHODS: From 2014 to 2019, 323 DE embryo transfers were completed in 200 recipients using oocytes derived of 163 donors. We assessed data for oocytes being freshly retrieved (FRESH-EGG) vs. purchased frozen (FROZEN-EGG); embryos transferred fresh (FRESH-ET) vs. frozen (FROZEN-ET); cycles SHARED (two recipients) vs. SOLE (one recipient); single (SET) vs. double (DET) embryo transfers and usage of PGT-A. Primary outcome was ongoing pregnancy plus live birth (OP/LB) rate. RESULTS: A total of 229 FRESH-EGG (70%) and 94 FROZEN-EGG (30%) cycles were completed. Overall, the use of FRESH-EGG yielded a higher OP/LB compared to FROZEN-EGG (49% vs. 30%, p = 0.001); within the FRESH-EGG group, OP/LB was similar when comparing FRESH-ET vs. FROZEN-ET (58% vs. 45%, p = 0.07). Within the FRESH-ET group, those using FRESH-EGG had a higher OP/LB than those using FROZEN-EGG (58% vs. 27%, p < 0.001). SHARED vs. SOLE cycles (p = 0.6), donor age (21-32 years; p = 0.4), and age of intended parents (maternal p = 0.3, paternal p = 0.2) did not significantly impact OP/LB. Notably, the use of PGT-A did not improve odds for an OP/LB (p = 0.7). CONCLUSION: The use of FRESH-EGG with FRESH-ET without PGT-A remains superior to newer DE treatment combinations. Specifically, the use of FROZEN-EGG and PGT-A did not improve outcomes. Although changing DE practices may enhance experience and affordability, patients and providers must appreciate that choices do not always favorably impact success. Additionally, newly available genetic-ancestry testing may pose longer-term ramifications mandating change in treatment and/or counseling.

Endometrial compaction does not predict live birth rate in single euploid frozen embryo transfer cycles.

PURPOSE: To evaluate whether endometrial compaction using sequential transvaginal ultrasound is associated with improved live birth rates in medicated single euploid frozen embryo transfer (FET) cycles. METHODS: Prospective observational cohort study at a private fertility clinic. Patients who underwent FETs between January and December 2018 were assessed for inclusion. The change in endometrial thickness between the end of the estrogen phase and the day before embryo transfer, measured by sequential transvaginal ultrasound, was used to categorize cycles with compaction (≥ 5%), no change, or expansion (≥ 5%). FET cycle outcomes were then compared between groups. The primary outcome was live birth. Secondary outcomes include clinical pregnancy rate and rate of spontaneous abortion. RESULTS: Of the 259 single euploid medicated FETs performed during the study period, only 43/259 (16.6%) of the cycles demonstrated ≥ 5% compaction, whereas 152/259 (58.7%) expanded and 64/259 (24.7%) were unchanged. Live birth rates did not differ between cycles with compaction (58.1%), no change (54.7%), or expansion (58.6%), p = 0.96. Clinical pregnancy and spontaneous abortion rates were also similar between groups. CONCLUSION: The vast majority of cycles did not demonstrate endometrial compaction. Endometrial compaction is not associated with live birth rate or spontaneous abortion rate in medicated single euploid FETs in this cohort.

Does hysteroscopic resection of uterine septum improve reproductive outcomes: a systematic review and meta-analysis.

PURPOSE: Uterine septum in women with subfertility or previous poor reproductive outcomes presents a clinical dilemma. Hysteroscopic septum resection has been previously associated with adverse reproductive outcomes but the evidence remains inconclusive. We aimed to thoroughly and systematically appraise relevant evidence on the impact of hysteroscopically resecting the uterine septum on this cohort of women. METHODS: AMED, BNI, CINAHL, EMBASE, EMCARE, Medline, PsychInfo, PubMed, Cochrane register of controlled trials, Cochrane database of systematic reviews and CINAHL were assessed to April 2020, with no language restriction. Only randomised control trials and comparative studies which evaluated outcomes in women with uterine septum and a history of subfertility and/or poor reproductive outcomes treated by hysteroscopic septum resection against control were included. The primary endpoint was live birth rate, whereas clinical pregnancy, miscarriage, preterm birth and malpresentation rates were secondary outcomes. RESULTS: Seven studies involving 407 women with hysteroscopic septum resection and 252 with conservative management were included in the meta-analysis. Hysteroscopic septum resection was associated with a lower rate of miscarriage (OR 0.25, 95% CI 0.07-0.88) compared with untreated women. No significant effect was seen on live birth, clinical pregnancy rate or preterm delivery. However, there were fewer malpresentations during labour in the treated group (OR 0.22, 95% CI 0.06-0.73). CONCLUSION: Our review found no significant effect of hysteroscopic resection on live birth. However, given the limited evidence available, high-quality randomised controlled trials are recommended before any conclusive clinical guidance can be drawn.

Modified endometriosis fertility index is more accurate to predict the non-ART pregnancy rate following surgery: a cohort of Chinese women.

OBJECTIVE: To examine whether a modified endometriosis fertility index (EFI) can better predict the rate of pregnancy without assisted reproductive technologies (ART) after laparoscopic surgery in infertile Chinese women with endometriosis. METHODS: 564 infertile women undergoing laparoscopy for endometriosis were retrospectively collected from January 2014 to December 2018. 472 patients were used to modify the EFI based on new, optimal cutoffs for its predictor variables. The predictive accuracy of the modified EFI was examined in the other 92 patients. RESULTS: Among the patients for the EFI modification, the multivariable Cox regression results showed that historical factors made more contribution in predicting non-ART pregnancy rate than surgical factors both in modified EFI (C-index: historical factors 0.617 vs surgical factors 0.558) and original EFI (C-index: historical factors 0.600 vs surgical factors 0.549). No significant relationship between the prior pregnancy and post-operative non-ART pregnancy rates was detected by both modified EFI and original EFI (p = 0.530 and 0.802, respectively). To assess the predictive effect of modified EFI, the two versions of modified EFI not only had higher predictive accuracy (C-index: 0.627 and 0.632) for non-ART pregnancy rates than that of the original EFI (C-index: 0.602) in the patients undergoing surgery during 2014-2017, but also higher than that of the original EFI (C-index: 0.638 and 0.612 vs 0.560) in the externally validated population in 2018. CONCLUSIONS: A modified EFI based on population-specific optimal cutoffs and weights might be more suitable for estimating the rate of non-ART pregnancy after laparoscopic surgery in infertile women with endometriosis.

Assisted reproductive technology outcome in United States of America and Australia with New Zealand: comparison of annual reports 2005-2016.

In vitro fertilization can be considered as causative factor of increasing rate of multiple pregnancies. Analysis of factors contributing to reduction in the percentage of multiple pregnancies may contribute to overall improvement of ART results. We compared annual reports from The Australian and New Zealand Assisted Reproduction Database and US National Summary Reports presented by The Centers for Disease Control and Prevention. The aim of this study was to analyze results of ART outcomes in two countries presenting opposite approach to ART, particularly to number of transferred embryos and number of eSETs (elective single embryo transfers). We found significant increase in total number of initiated cycles and transfers with significant shift toward frozen cycles and transfers in both countries. Percentage of eSET increased while average number of embryos transferred per one transfer decreased significantly in both countries without significant difference between countries. We also noticed significant decrease in the rate of multiple pregnancies and percentage of pregnancies resulting in triplets in Australia with New Zealand. Decreasing number of multiple pregnancies and higher percentage of transfers and pregnancies resulting in singleton live birth are the changes in ART politics found in our analysis. United States of America have more significant changes toward eSET, although Australia and New Zealand have significantly higher percentage of eSET from the beginning of analysis.

Recurrent implantation failure: which patients benefit from endometrial scratching prior to IVF?

PURPOSE: Endometrial scratching (ES) using a biopsy catheter prior to the IVF cycle in the repeated implantation failure (RIF) population has been suggested, but no convincing evidence of its benefit has been presented until now. METHODS: A retrospective mono-center study among 300 consecutive IVF-RIF cycles following evaluation of the ovarian reserve, hysterosalpingography or hysteroscopy, pelvic ultrasound, thrombophilia evaluation, karyotyping and assessment of male sperm parametrs. The findings within normal limits. All the patients offered ES, 78 consented and underwent ES prior to their next IVF cycle. RESULTS: A comparison of treatment outcomes between the post-ES cycles (n = 78) and the non-ES cycles (222) demonstrated the following: 34 (43.5%) versus 14 (6.3%) conceptions, respectively (p = 0.001) and 30 (38.4%) versus 2 (0.9%) clinical pregnancies, respectively (p < 0.001%), emphasizing an extremely high biochemical pregnancy rate among the non-ES cycles. Implantation rate was 19.7% versus 0.4%, respectively (p < 0.001) and live birth rate was 33.33% (26 newborns) versus 0.45% (1 newborn), respectively (p < 0.001). Since there were more embryos available for transfer and more top-quality embryos in the post-ES-IVF conception cycles, the role of ES became questionable. A multivariate analysis that included ES and the percentage of top-quality embryos demonstrated that ES was an independent factor highly correlated with conception in this particular RIF population. CONCLUSIONS: ES proved to be an efficient tool in a particular subgroup of RIF patients with fertility investigation results within normal limits, an optimal ovarian response to gonadotropins, and a high percentage of top-quality embryos. Nevertheless, the results should not be overestimated, since the study has limitations related to its retrospective model.

Cross-linked hyaluronan gel to improve pregnancy rate of women patients with moderate to severe intrauterine adhesion treated with IVF: a randomized controlled trial.

PURPOSE: To evaluate whether the cross-linked hyaluronan (cHA) gel can improve the clinical pregnancy rate of patients with moderate to severe intrauterine adhesion (IUA) who underwent operative hysteroscopy followed by embryo transfer. METHODS: Women with moderate to severe IUA desiring to undergo embryo transfer were recruited in this randomized controlled trial. The patients were randomized on the day of receiving hysteroscopy. The control group received standard hysteroscopy, while cHA gel was applied to the treatment group at the end of hysteroscopy and 5-7 days after operation. All patients were expected to undergo in vitro fertilization (IVF)/intracytoplasmic sperm injection and frozen-thawed embryo transfer (FET). RESULTS: A total of 306 patients were enrolled in this study, of which 202 were assigned to the treatment group and 104 to the control group. Both the clinical pregnancy rate (26.3% [49/186] vs. 15.3% [13/85], P = 0.045), the implantation rate (17.7% [57/322] vs. 9.8% [15/153], P = 0.025), and the endometrial thickness on the day of embryo transfer (7.97 ± 1.37 vs. 7.50 ± 0.60 mm, P < 0.001) were significantly higher in the treatment group compared to the control group. In addition, histological assessment of the paired endometrial tissues collected before and after operation revealed a relatively higher number of tubular glands after operation (15.1 ± 13.2 vs. 28.8 ± 30.4, P = 0.166). CONCLUSIONS: To conclude, the application of cHA gel in patients with moderate to severe IUA during hysteroscopy can improve the quality of endometrium and uterine receptivity and consequently enhance the clinical pregnancy rate after IVF/CSI and FET.

Effect of body mass index on pregnancy outcomes in a freeze-all policy: an analysis of 22,043 first autologous frozen-thawed embryo transfer cycles in China.

BACKGROUND: Abnormal BMI is associated with discouraging IVF outcomes in fresh autologous or oocyte donor cycles, whether or not such a relation also holds true for women undergoing frozen-thawed embryo transfer (FET) remains unknown. In addition, it remains unclear the detrimental effect of abnormal BMI on IVF outcomes occurs at the level of ovary or endometrium. METHODS: A retrospective study involved 22,043 first FET cycles of all women who had undergone a freeze-all policy during the period from January 2010 to June 2017. To control for the embryo factor, our analysis was restricted to women with high-quality embryo transfer. The main outcome measure was live birth rate per embryo transfer. The secondary endpoints included rates of implantation, clinical pregnancy, multiple pregnancy, and pregnancy loss. Multivariate logistic regression analysis was performed to detect the independent effect of BMI on live birth rate after adjusting for important confounding variables. RESULTS: In the crude analysis, reproductive outcomes were similar between underweight women and normal-weight controls whereas all parameter outcomes were significantly worse in patients with obesity. After adjustment for a number of confounding factors, underweight women had a marginally significant decrease in rates of implantation (adjusted odds ratio (aOR) 0.91; 95% CI 0.85-0.96), clinical pregnancy (aOR 0.91; 95% CI 0.83-0.99), and live birth (aOR 0.91; 95% CI 0.83-0.99) as compared to the women with normal weight. Obesity was significantly associated with decreased implantation (aOR 0.80; 95% CI 0.73-0.87), clinical pregnancy (aOR 0.81; 95% CI 0.71-0.91), and live birth rates (aOR 0.70; 95% CI 0.62-0.80). Moreover, the pregnancy loss rate, both in the first (aOR 1.46; 95% CI 1.15-1.87) and in the second trimester (aOR 2.76; 95% CI 1.67-4.58), was significantly higher in the obesity group than that in the reference group. CONCLUSIONS: Among women undergoing first FET with high-quality embryo transfer, low BMI has limited impact on pregnancy and live birth rates. On the contrary, obesity was associated with worse IVF outcomes. Our findings further highlighted that endometrial receptivity played an important role in the poor reproductive outcomes of women with abnormal weight status.

Pregnancy rate and outcome of pregnancies in long-term survivors of Hodgkin's lymphoma.

Thanks to the increased number of young survivors of Hodgkin's lymphoma (HL), management of the pregnancies of women who have a history of exposure to chemotherapies and radiation therapy is becoming increasingly common. Many patients and clinicians are worried that pregnancy after the diagnosis of HL may increase the risk of relapse, despite a lack of empirical evidence to support such concerns. In the present study, we included 89 women diagnosed with HL between 2006 and 2015 under the age of 50 years, who were in complete remission and alive without relapse > 1 year after treatment. We determined the pregnancy rate, time to pregnancy, and the disease-free survival. We found no evidence of significant impairment of the fertility of female HL long-term survivors and no evidence that a pregnancy increases the relapse rate among women in remission from HL. Survivors of HL need to consider a range of factors when deciding on future reproduction.

Effectiveness on fertility outcome of tubal flushing with different contrast media: systematic review and network meta-analysis.

OBJECTIVES: To compare, in women with infertility, the effectiveness and safety of tubal flushing using oil-based contrast medium, water-based contrast medium or their combination, and no tubal flushing, and to evaluate the effectiveness of tubal flushing on fertility outcome over time. METHODS: We performed a systematic review and network meta-analysis, searching the electronic databases MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials, and trial registries, up to 25 September 2018. We included randomized controlled trials (RCTs) comparing the following interventions with each other or with no intervention in women with infertility: tubal flushing using water-based contrast medium, tubal flushing using oil-based contrast medium or additional tubal flushing with oil-based medium following diagnostic tubal flushing with water-based medium. The outcomes included clinical pregnancy, live birth, ongoing pregnancy, miscarriage, ectopic pregnancy and adverse events. RESULTS: Of the 283 studies identified through the search, 14 RCTs reporting on 3852 women with infertility were included. Network meta-analysis showed that tubal flushing using oil-based contrast medium was associated with higher odds of clinical pregnancy within 6 months after randomization and more subsequent live births compared with tubal flushing using water-based medium (odds ratio (OR), 1.67 (95% CI, 1.38-2.03), moderate certainty of evidence; and OR, 2.18 (95% CI, 1.30-3.65), low certainty of evidence, respectively) and compared with no intervention (OR, 2.28 (95% CI, 1.50-3.47), moderate certainty of evidence; and OR, 2.85 (95% CI, 1.41-5.74), low certainty of evidence, respectively). These results agreed with those of the pairwise meta-analysis. For clinical pregnancy within 6 months, there was insufficient evidence of a difference between tubal flushing with water-based contrast medium and no intervention (OR, 1.36 (95% CI, 0.91-2.04), low certainty of evidence). For fertility outcomes after 6 months, there was insufficient evidence of a difference in any comparison (low to very low certainty of evidence). Compared with tubal flushing using water-based contrast medium, the use of oil-based contrast medium was associated with higher odds of asymptomatic intravasation (OR, 5.06 (95% CI, 2.29-11.18), moderate certainty of evidence). CONCLUSIONS: In women with infertility undergoing fertility workup, tubal flushing using oil-based contrast medium probably increases clinical pregnancy rates within 6 months after randomization and may increase subsequent live-birth rates, compared with tubal flushing using water-based contrast medium and compared with no intervention. Evidence on fertility outcomes beyond 6 months is inadequate to draw firm conclusions. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Eficacia sobre el resultado de fertilidad del lavado de trompas con diferentes medios de contraste: revisión sistemática y metaanálisis en red OBJETIVOS: Comparar, en mujeres con infertilidad, la efectividad y seguridad del lavado de trompas con un medio de contraste a base de aceite, un medio de contraste a base de agua o una combinación, y el no lavado de trompas, y evaluar la efectividad del lavado de trompas en el resultado de la fertilidad con el tiempo. MÉTODOS: Se realizó una revisión sistemática y un metaanálisis en red, mediante búsquedas en las bases de datos electrónicas MEDLINE, EMBASE y el Registro Central Cochrane de Ensayos Controlados, y en otros registros de ensayos, hasta el 25 de septiembre de 2018. Se incluyeron ensayos controlados aleatorizados (ECA) que compararon las siguientes intervenciones entre sí o con la no intervención en mujeres con infertilidad: lavado de trompas con medio de contraste a base de agua, lavado de trompas con medio de contraste a base de aceite o lavado de trompas adicional con un medio a base de aceite después de un lavado de trompas con un medio a base de agua. Los resultados incluyeron el embarazo confirmado ecográficamente, el nacimiento vivo, el embarazo en curso, el aborto espontáneo, el embarazo ectópico y los eventos adversos. RESULTADOS: De los 283 estudios identificados mediante la búsqueda, se incluyeron 14 ECA que informaron sobre 3852 mujeres con infertilidad. El metaanálisis en red mostró que el lavado de trompas con medio de contraste a base de aceite se asoció con mayores probabilidades de embarazo confirmado ecográficamente dentro de los seis meses posteriores a la aleatorización y más nacimientos vivos posteriores en comparación con el lavado de trompas con medio a base de agua (razón de momios [RM], 1,67; IC 95%: 1,38-2,03), certeza moderada de evidencia; y RM, 2,18 (IC 95%: 1,30-3,65), certeza baja de evidencia, respectivamente) y en comparación con la no intervención (RM, 2,28 (IC 95%: 1,50-3,47), certeza moderada de evidencia; y RM, 2,85 (IC 95%: 1,41-5,74), certeza baja de evidencia, respectivamente). Estos resultados coincidieron con los del metaanálisis por pares. No hubo evidencia suficiente de una diferencia entre el lavado de trompas con medio de contraste a base de agua y la no intervención para el embarazo clínico dentro de los seis meses (RM, 1,36 (IC 95%: 0,91-2,04); certeza baja de evidencia). Para los resultados de fertilidad después de los seis meses, no hubo evidencia suficiente de diferencias en cualquier comparación (certeza de evidencia baja a muy baja). En comparación con el lavado de trompas con un medio de contraste a base de agua, el uso de un medio de contraste a base de aceite se asoció con mayores probabilidades de intravasación asintomática (RM, 5,06 (IC 95%: 2,29-11,18), certeza moderada de evidencia). CONCLUSIONES: En las mujeres con infertilidad que se someten a un examen de fertilidad, el lavado de trompas con medio de contraste a base de aceite aumenta la probabilidad de las tasas de embarazo clínico dentro de los 6 meses posteriores a la aleatorización y puede aumentar las tasas posteriores de nacimientos vivos, en comparación con el lavado de trompas con medio de contraste a base de agua y en comparación con la no intervención. La evidencia sobre los resultados de fertilidad después de los seis meses es inadecuada para establecer conclusiones firmes. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Effects of growth hormone on pregnancy rates of patients with thin endometrium.

PURPOSE: To investigate whether growth hormone (GH) could improve pregnancy rates of patients with thin endometrium by clinical study and laboratory experiments. MATERIALS AND METHODS: Ninety-three patients were randomized to either the GH-received group (40) or the routine exogenous administration of estrogens control group (53) for clinical study. The human endometrial carcinoma cell line RL95-2 was used for testing the role of GH with Western blot and real-time PCR by exposure to various concentrations of GH (0.1 nM,1 nM,10 nM,100 nM). RESULTS: Patients treated with GH had a significantly (P < 0.05) greater endometrium thickness on day 3 (7.87±0.72 vs 6.34±0.86), higher implantation rates (24.4% vs 10.5%) and greater clinical pregnancy rates (42.5% vs 18.9%) compared with the control group. No adverse events were associated with the use of GH. Administration of GH significantly up-regulated the expression of VEGF, ItgB3 and IGF-I expression in RL95-2 cells at both mRNA and protein levels (P < 0.05). AG490, an inhibitor of JAK2, nearly completely inhibited the up-regulative effect of GH through the JAK2-STAT5 pathway, and GH-induced effects could be mediated through autocrine IGF-I together with its hepatic counterpart. IGF-I mRNA was detected in the RL95-2 cells. CONCLUSION: GH may improve pregnancy outcomes of patients with thin endometrium who undergo frozen embryo transfer by acting on human endometrial cells to promote proliferation and vascularization and to up-regulate receptivity-related molecular expression.