Effects of hepatitis B virus infection on the treatment outcomes following in vitro fertilization/intracytoplasmic sperm injection: An analysis of 21,999 first embryo transfer cycles.

To investigate the effects of hepatitis B virus (HBV) infection on the outcomes of Chinese couples undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) and the clinical data of their neonates. A total of 21,999 first embryo transfer cycles were included. They were categorized into four groups based on the couple's hepatitis B surface antigen (HBsAg) result (Group A = female HBsAg- and male HBsAg- ; Group B = female HBsAg+ and male HBsAg- ; Group C = female HBsAg- and male HBsAg+ ; Group D = female HBsAg+ and male HBsAg+ ). The fertilization rate (FR), cleavage rate (CR), implantation rate (IPR), clinical pregnancy rate (CPR), live birth rate (LBR) and miscarriage rate (MCR) were analysed. Multilevel logistic regression was applied to evaluate the association. The total prevalence of HBV infection was 5.74% (2526/43998). There were no statistically significant differences in CRs (98.69%, 98.76%, 98.66%, 98.72%, p > .05), IPRs (45.86%, 47.33%, 45.19%, 39.61%, p > .05), CPRs (62.84%, 65.05%, 61.80%, 56.81%, p > .05), MCRs (12.70%, 11.99%, 12.58%, 4%, p > .05) and LBRs (53.43%, 55.38%, 52.70%, 54.54%, p > .05) among the four groups. However, there were significant differences in FRs (66.25%, 66.55%, 66.32%, 61.92%, p < .05). Group D had the lowest FR. After adjusting for confounders, the multilevel logistic regression showed that HBsAg+ had no impact on the LBR, CPR or MCR. We also analysed the data of 14,465 newborns, including 8593 singletons and 2936 twins. Among the four groups, no variables reached statistical significance, including neonatal birth weight (NBW), twin ratio, gestational age, premature birth, delivery type, fetal macrosomia or low birth weight (p > .05). Our study demonstrates that, although biparental HBV infection may affect the FR, neither single-parent infection nor biparental HBV infection affects IVF/ICSI outcomes or neonatal outcomes.

Body mass index impacts ectopic pregnancy during in vitro fertilization: an analysis of 42,362 clinical pregnancy cycles.

PURPOSE: This large, single-center, retrospective cohort study was aimed to explore the effect of female body mass index (BMI) on ectopic pregnancy (EP) following fresh and frozen-thawed embryo transfers (ET). METHODS: A total of 27,600 pregnancies after fresh ET and 14,762 pregnancies after frozen-thawed ET were included between January 2010 to June 2022. Women were divided into three groups based on BMI according to the Working Group on Obesity in China (WGOC), International Life Sciences Institute (ILSI): underweight (BMI < 18.5 kg/m2), normal weight (BMI, 18.5-23.9 kg/m2), and overweight or obesity (≥ 24 kg/m2). Compare EP rates among BMI categories in fresh and frozen-thawed ET cycles respectively. Multivariate logistic regression analyses were used to investigate the association between female BMI and EP. RESULTS: The overall EP rates in fresh, and frozen thawed transfer cycles were 2.43% (672/27,600) and 2.82% (417/14,762), respectively. In fresh ET cycles, underweight women yielded a significantly higher EP rate than those with normal and excess weight (3.29% vs. 2.29% vs. 2.54%, P = 0.029). But EP rates did not differ among the three BMI groups (2.72% vs. 2.76% vs. 2.96%, P = 0.782) in frozen-thawed ET cycles. In fresh ET cycles, after adjusting for potential confounding factors, no significant association was found between female BMI and EP occurrence (adjusted OR: 0.98, 95% CI 0.70-1.37, P = 0.894, for BMI 18.5-23.9 kg/m2; adjusted OR: 0.89, 95% CI 0.75-1.06, P = 0.205, for BMI ≥ 24 kg/m2. Reference = BMI < 18.5 kg/m2). CONCLUSION(S): Female BMI did not affect the occurrence of ectopic pregnancy in either fresh or frozen-thawed embryo transfer cycles.

The reference value of anti-Müllerian hormone to diagnose polycystic ovary syndrome is inversely associated with BMI: a retrospective study.

BACKGROUND: This study aimed to evaluate the cut-off value of anti-Müllerian hormone (AMH) combined with body mass index (BMI) in the diagnosis of polycystic ovary syndrome (PCOS) and polycystic ovary morphology (PCOM). METHODS: This retrospective study included 15,970 patients: 3775 women with PCOS, 2879 women with PCOM, and 9316 patients as controls. Multivariate logistic regression analysis was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for AMH. We randomly divided the patients into two data sets. In dataset 1, a receiver operating characteristic (ROC) curve was generated to analyze the accuracy of basic AMH levels in diagnosing PCOS and PCOM. The optimal cut-off value was calculated in dataset 1 and validated in dataset 2, expressed as sensitivity and specificity. RESULTS: In the PCOS group, obese patients had the lowest AMH levels, while underweight patients had the highest AMH level (P < 0.001). After adjusting for age, the ratio of luteinizing hormone (LH) and follicle stimulating hormone (FSH), serum testosterone level, and BMI, AMH was an independent predictor of PCOS and PCOM. In the group with BMI < 18.5 kg/m2, the optimistic AMH cut-off value was 5.145 ng/mL with a sensitivity of 84.3% and specificity of 89.1%, whereas in the BMI ≥ 28 kg/m2 group, the optimistic AMH cut-off value was 3.165 ng/mL with a sensitivity of 88.7% and specificity of 74.6%. For the BMI range categories of 18.5-24, 24.0-28 kg/m2, the optimistic AMH cut-off values were 4.345 ng/mL and 4.115 ng/mL, respectively. The tendency that the group with lower weight corresponded to higher AMH cut-off values was also applicable to PCOM. In the same BMI category, patients with PCOM had a lower AMH diagnosis threshold than those with PCOS (< 18.5 kg/m2, 5.145 vs. 4.3 ng/mL; 18.5-24 kg/m2, 4.345 vs. 3.635 ng/mL; 24.0-28 kg/m2, 4.115 vs. 3.73 ng/mL; ≥ 28 kg /m2, 3.165 vs. 3.155 ng/mL). These cut-off values had a good diagnostic efficacy in the validation dataset. Based on different phenotypes and severity of ovulation disorders, the distribution of AMH in PCOS were also significantly different (P < 0.001). CONCLUSIONS: AMH is a potential diagnostic indicator of PCOS and is adversely associated with BMI. The AMH cut-off value for diagnosing PCOS was significantly higher than that for PCOM.

Polycystic ovary syndrome increases the rate of early spontaneous miscarriage in women who have undergone single vitrified euploid blastocyst transfer.

RESEARCH QUESTION: Does polycystic ovary syndrome (PCOS) independently influence the risk of early spontaneous miscarriage in patients undergoing single euploid vitrified blastocyst transfer? DESIGN: This observational cohort study retrospectively analysed 1498 patients undergoing their first single euploid blastocyst frozen transfer cycles between October 2016 and December 2021. Patients were divided into PCOS and non-PCOS groups according to the Rotterdam criteria. Logistic regression analysis was conducted to study the independent effect of maternal PCOS status on early spontaneous miscarriage after single euploid embryo transfer after adjusting for confounding factors. RESULTS: No statistically significant differences were identified in the rates of positive pregnancy test (68.95% versus 64.86%, P = 0.196) or clinical pregnancy (59.93% versus 57.33%, P = 0.429) between the PCOS and non-PCOS groups after single euploid embryo transfer. Early spontaneous miscarriage occurred more frequently in women with PCOS compared with controls (18.67% versus 12.00%, P = 0.023). In single euploid embryo transfer cycles, PCOS significantly increased the incidence of early spontaneous miscarriage after adjusting for some potential confounders (adjusted odds ratio 1.649, 95% CI 1.032 to 2.635, P = 0.036). CONCLUSIONS: Although no significant difference was observed in clinical pregnancy rates, PCOS status increased the risk of early spontaneous miscarriage after single vitrified euploid blastocyst transfer, suggesting an additional role of endometrial dysfunction affected by endocrine disorders. Further studies are needed to investigate the specific mechanisms and effective intervention strategies.

High sperm DNA fragmentation increased embryo aneuploidy rate in patients undergoing preimplantation genetic testing.

RESEARCH QUESTION: Is high sperm DNA fragmentation (SDF) associated with a high embryonic aneuploidy rate in patients undergoing intracytoplasmic sperm injection (ICSI)-preimplantation genetic testing (PGT)? DESIGN: This was a retrospective study of 426 couples with normal karyotypes undergoing ICSI-PGT at the authors' centre from March 2017 to March 2021. SDF was assessed using the sperm chromatin structure assay. The population was divided into low and high SDF groups according to cut-off values found by the receiver operating characteristic (ROC) curve. A 1:1 ratio propensity score matching (PSM) method was used to control for potential confounding factors, and a generalized linear mixed model was established to evaluate the relationship between SDF and the embryonic aneuploidy rate. RESULTS: The ROC curve indicated a threshold of 30%. In total, 132 couples were included after PSM, and the high SDF group (>30%) had significantly higher SDF (40.74% ± 9.78% versus 15.54% ± 7.86%, P < 0.001) and a higher embryo aneuploidy rate (69.36% versus 53.96%, P < 0.001) compared with the low SDF group (≤30%). The two pronuclear fertilization rate, cleavage rate, rate of high-quality embryos at day 3 rate, blastocyst rate, biochemical pregnancy rate, clinical pregnancy rate, miscarriage rate, live birth rate, caesarean section rate, preterm birth rate, singleton rate and low birthweight rate were similar in both groups (P > 0.05). After PSM, SDF > 30% was significantly correlated with an increased embryo aneuploidy rate after adjusting for all confounding variables (adjusted odds ratio 1.70, 95% CI 1.00-2.88, P = 0.049). CONCLUSIONS: SDF > 30% was associated with an increased embryo aneuploidy rate in couples with normal karyotypes undergoing PGT, but did not affect embryonic and clinical outcomes after transfer of euploid embryos.

Effect of blastocyst morphology on the incidence of monozygotic twinning pregnancy after single blastocyst transfer.

Aims: To explore whether blastocyst morphology [blastocyst stage, inner cell mass (ICM), and trophectoderm (TE) grading] impacts the occurrence of monozygotic twinning (MZT) after single blastocyst transfer (SBT).Materials and methods: A single-center retrospective cohort study was conducted including all clinical pregnancies after single blastocyst transfer between January 2015 and September 2021 (n = 9229). Blastocyst morphology was assessed using Gardner grading system. MZT was defined as more than one gestational sac (GS), or two or more fetal heartbeats in a single GS via ultrasound at 5-6 gestational weeks.Results: The overall MZT rate was 2.46% (227 of 9229 cases), of which was the highest in blastocysts of grade A TE and lowest in those with grade C TE (grade A: B:C = 3.40%:2.67%:1.58%, p = .002). Higher risk of MZT pregnancy was associated with higher trophectoderm grading [A vs. C: aOR, 1.883, 95% CI 1.069-3.315, p = .028; B vs C: aOR, 1.559, 95% CI 1.066-2.279, p = .022], but not extended culture in vitro (day 5 vs. day 6), vitrification (fresh vs. frozen-thawed ET), assisted hatching (AH), blastocyst stage (stage 1-6) or ICM grading (A vs. B).Conclusions: We conclude that TE grade is an independent risk factor of MZT after single blastocyst transfer. Blastocysts with high-grade trophectoderm are more liable to obtain monozygotic multiple gestation.

Are ovarian responses and the number of transferable embryos different in females and partners of male balanced translocation carriers?

PURPOSE: To compare ovarian response and the number of transferable embryos between women with balanced autosomal translocations and women whose partners carry the translocation (control group). To investigate the predictive value of metaphase II (MII) oocyte number and biopsied embryo number for gaining at lowest one transferable embryo. DESIGN: We retrospectively analyzed 1942 preimplantation genetic testing for structural rearrangements (PGT-SR) cycles of 1505 balanced autosomal translocation couples over 8 years. All cycles were divided into two subgroups: Robertsonian and reciprocal translocations (ROBT and ReBT). Receiver operator characteristic (ROC) curves were plotted to ascertain a cutoff of MII oocytes and biopsied embryos as predictors of gaining at lowest one transferable embryo. RESULT: There were no statistical differences in baseline features or ovarian response indicators regarding the number of retrieved/MII oocytes, E2 level on the day of HCG, and ovarian sensitivity index (OSI) between women with balanced autosomal translocations and control group (P > 0.05). A decreased number of transferable embryos were found in women with balanced autosomal translocations regardless of the type of translocation. The cutoff values for gaining at lowest one transferable embryo are 12.5 MII oocytes and 4.5 biopsied embryos, respectively. CONCLUSION: Women with balanced autosomal translocations have a normal ovarian response, but fewer transferable embryos, meaning that higher gonadotropin (Gn) doses may be required to increase transferable embryos. When fewer than 12.5 MII oocytes or 4.5 blastocysts are obtained in a PGT-SR cycle, couples should be notified that the likelihood of gaining a transferable embryo is low.

Effect of endometrial thickness changes on clinical pregnancy rates after progesterone administration in a single frozen-thawed euploid blastocyst transfer cycle using natural cycles with luteal support for PGT-SR- and PGT-M-assisted reproduction: a retrospective cohort study.

BACKGROUND: To investigate whether the endometrial thickness change ratio from the progesterone administration day to the blastocyst transfer day is associated with pregnancy outcomes in a single frozen-thawed euploid blastocyst transfer cycle. METHODS: All patients used natural cycles with luteal support for endometrial preparation and selected a single euploid blastocyst for transfer after a biopsy for preimplantation genetic testing. The endometrial thickness was measured by transvaginal ultrasound on the progesterone administration day and the transfer day, the change in endometrial thickness was measured, and the endometrial thickness change ratio was calculated. According to the change rate of endometrial thickness, the patients were divided into three groups: the endometrial thickness compaction group, endometrial thickness non-change group and endometrial thickness expansion group. Among them, the endometrial thickness non-change and expansion groups were combined into the endometrial thickness noncompaction group. RESULTS: Ultrasound images of the endometrium in 219 frozen-thawed euploid blastocyst transfer cycles were evaluated. The clinical pregnancy rate increased with the increase in endometrial thickness change ratio, while the miscarriage rate and live birth rate were comparable among the groups. The multiple logistic regression results showed that in the fully adjusted model a higher endometrial thickness change ratio (per 10%) was associated with a higher clinical pregnancy rate (adjusted odds ratio [aOR] 1.29; 95% confidence interval [CI], 1.01-1.64; P = .040). Similarly, when the patients were divided into three groups according to the change rate of endometrial thickness, the endometrial thickness noncompaction group had a significant positive effect on the clinical pregnancy rate compared with the endometrial thickness compaction group after adjusting for all covariates. CONCLUSIONS: In frozen-thawed euploid blastocyst transfer cycles in which the endometrium was prepared by natural cycles with luteal support, the clinical pregnancy rate was higher in cycles without endometrial compaction after progesterone administration.

Live birth rates after natural cycle versus hormone replacement therapy for single euploid blastocyst transfers: a retrospective cohort study.

RESEARCH QUESTION: Is there any difference in live birth rate between the natural cycle and hormone replacement therapy (HRT) endometrial preparation protocols for women with regular menstrual cycles undergoing their first single vitrified-warmed euploid blastocyst transfer? DESIGN: This was a retrospective cohort study that enrolled 722 women who underwent vitrified-warmed euploid blastocyst transfer at assisted reproductive technology (ART) centre of The First Affiliated Hospital of Zhengzhou University, from January 2013 to December 2019. Univariate and multivariate logistic regression models were used to analyse the relationship between the endometrial preparation protocols and live birth rates. Stratified analyses and sensitivity analyses were performed to ensure the reliability and stability of the results. RESULTS: A total of 722 single vitrified-warmed euploid blastocyst transfer cycles were included. Overall, the live birth rates were 50.00% (110/220) in the natural cycle group and 47.61% (239/502) in the HRT group. Multiple logistic regression analyses showed that there was no significant association (adjusted odds ratio 0.82; 95% confidence interval 0.56-1.20; P = 0.313) between natural cycle and HRT protocols and the live birth rate. Interaction analysis showed that there was no significant difference in live birth rates between the two groups for any subgroup after adjusting for confounding factors. CONCLUSIONS: For single vitrified-warmed euploid blastocyst transfer, natural cycle and HRT endometrial preparation protocols result in similar live birth rates among women with regular menstrual cycles. Further studies are needed into the effects of endometrial preparation protocols on pregnancy outcomes.

Ambient air pollutant exposure and in vitro fertilization treatment outcomes in Zhengzhou, China.

OBJECTIVE: To study the association between ambient air pollutant exposure during the follicular phase and in vitro fertilization (IVF) outcomes. DESIGN: A single-center retrospective analysis. SETTING: Henan Province, China. PATIENTS: Patients (n = 6659) living in Zhengzhou, Henan Province in central China who underwent their first IVF cycle at the First Affiliated Hospital of Zhengzhou University between 2013 and 2019 were included for analysis. INTERVENTION: None. MAIN OUTCOME MEASURE: The relationships between PM2.5, PM10, and AQI (Air Quality Index) with IVF outcomes during the follicular phase (period I, 85 days before oocyte retrieval; period II, gonadotrophin start to oocyte retrieval). RESULTS: Compared with the bottom tertile, exposure to the top PM2.5 and PM10 tertiles during period I was associated with decreased clinical pregnancy (PM2.5: adjusted odds ratio [OR], 0.838%, and 95% confidence interval [CI], 0.723 and 0.971; PM10: adjusted OR, 0.818%, and 95% CI, 0.705 and 0.950), and decreased live birth rate (PM2.5: adjusted odds ratio [OR], 0.852%, and 95% confidence interval [CI], 0.736 and 0.987; PM10: adjusted OR, 0.850%, and 95% CI, 0.733 and 0.986), and exposure to the top PM2.5 tertile during period II adversely affected clinical pregnancy and the live birth rate (adjusted OR, 0.824%, and 95% CI, 0.711 and 0.955; adjusted OR, 0.817%, and 95% CI, 0.706 and 0.945). Compared with the bottom PM10 tertile, exposure to the middle PM10 tertile in period II showed decreased clinical pregnancies and live births (adjusted OR, 0.844; 95% CI, 0.729 and 0.978, adjusted OR, 0.846; 95% CI, 0.731 and 0.979). The PM10 level during period II of the follicular phase tend to adversely affect live birth rate, but the tendency did not reach significance (P = 0.051). CONCLUSION: Exposure to PM2.5 and PM10 before oocyte retrieval has an adverse effect on IVF outcomes. CAPSULE: Exposure to PM2.5 and PM10 before oocyte retrieval has an adverse effect on IVF outcomes.

Factors related to early spontaneous miscarriage during IVF/ICSI treatment: an analysis of 21,485 clinical pregnancies.

RESEARCH QUESTION: Which factors are related to early spontaneous miscarriage in IVF-conceived clinical pregnancies? DESIGN: A total of 21,485 clinical pregnancies were included in the analysis. First, early spontaneous miscarriage rates were compared among different groups according to female age, body mass index (BMI), number of previous miscarriages, infertility diagnosis and type and cycle characteristics. Then, the spontaneous miscarriage rate in patients with polycystic ovary syndrome (PCOS), uterus malformation and endometriosis was compared with that in patients with male factor infertility alone. Last, logistic regression was used to analyse factors affecting the early spontaneous miscarriage rate. RESULTS: Of the 21,485 cycles, 2703 cycles (12.58%) resulted in early spontaneous miscarriage. In patients <35 years old, those with uterus malformation or PCOS experienced significantly higher spontaneous miscarriage rates (14.44% versus 9.47%, P = 0.027; 11.43% versus 9.47%; P = 0.003) compared with controls (male factor only). In multivariate logistic regression analysis, the spontaneous miscarriage rate increased in frozen embryo transfer cycles in patients <35 years old (odds ratio [OR] 1.449, 95% confidence interval [CI] 1.303-1.611, P = 0.000), but decreased in patients ≥35 years old (OR 0.794, 95% CI 0.671-0.939, P = 0.007) compared with fresh cycles. CONCLUSIONS: Female age, number of previous miscarriages and endometrial thickness on the day of embryo transfer were independent factors associated with early spontaneous miscarriage. PCOS, uterus malformation and frozen embryo transfer significantly increased spontaneous miscarriage rate in patients <35 years old compared with male factor alone controls. However, frozen embryo transfer decreased the spontaneous miscarriage rate in patients ≥35 years old compared with fresh cycles.

The impact of endometrial thickness change after progesterone administration on pregnancy outcome in patients transferred with single frozen-thawed blastocyst.

BACKGROUND: The aim of this study was to explore the impact of endometrial thickness change after progesterone administration on pregnancy outcome in patients transferred with single frozen-thawed blastocyst. METHODS: This observational cohort study included a total of 3091 patients undergoing their first frozen-thawed embryo transfer (FET) cycles between April 2015 to March 2019. Endometrial thickness was measured by trans-vaginal ultrasound twice for each patient: on day of progesterone administration, and on day of embryo transfer. The change of endometrial thickness was recorded. RESULTS: Regardless of endometrial preparation protocol (estrogen-progesterone/natural cycle), female age, body mass index (BMI), and infertility diagnosis were comparable between patients with an increasing endometrium on day of embryo transfer and those without. However, clinical pregnancy rate increases with increasing ratio of endometrial thickness. Compared with patients with Non-increase endometrium, those with an increasing endometrium on day of embryo transfer resulted in significantly higher clinical pregnancy rate (56.21% vs 47.13%, P = 0.00 in estrogen-progesterone cycle; 55.15% vs 49.55%, P = 0.00 in natural cycle). CONCLUSIONS: In most patients, endometrial thickness on day of embryo transfer (after progesterone administration) increased or kept being stable compared with that on day of progesterone administration. An increased endometrium after progesterone administration was associated with better pregnancy outcome.

Efficacy and Safety of In Vitro Fertilization (IVF)/Intracytoplasmic Sperm Injection (ICSI) Among Patients with Endometriosis After a Shortened Protocol of Long-Term Pituitary Downregulation.

BACKGROUND Patients with endometriosis (EMs) are routinely advised to take GnRH-a for 3-6 months to improve the internal reproductive environment, but this may not be necessary. MATERIAL AND METHODS This retrospective study examined the effects of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) with shortened (n=311) or conventional (n=213) long-term pituitary downregulation in EMs patients between January 2013 and July 2017. RESULTS The 2 groups showed no significant differences in gonadotropin (Gn) dose, number of oocytes retrieved, or miscarriage rate. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels on the initiation day and the LH level on human chorionic gonadotropin (hCG) day (1.22±1.39 vs. 0.74±0.55 P=0.0026) were higher in the study group than in the control group. The cumulative live birth rates in the second cycle were 69.13% in the study group (95% confidence interval (CI), 64-74.27%) vs. 68.54% in the control group (95% CI, 62.31-74.78%, P=0.88, respectively). CONCLUSIONS This study showed that the shortened regimen and the ultralong regimen did not produce different pregnancy outcomes after ART, and the single-application, long-term GnRH-a protocol may serve as a cost-effective and safe treatment protocol for EMs patients.

A multi-center, randomized controlled clinical trial of the application of a shortened protocol of long-acting Triptorelin down-regulated prior to IVF/ICSI among patients with endometriosis: A protocol.

BACKGROUND: Endometriosis is the major cause of progressive pelvic pain and subfertility. Up to 50% of reproductive-age women suffer from pelvic pain. Endometriosis is a classic indication for IVF. Compared with women whose inability to procreate is caused by simple tubal infertility, women with endometriosis often have lower pregnancy rates following in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). The administration of gonadotrophin-releasing hormone (GnRH) agonists prior to IVF/ICSI can improve the successful pregnancy rate. Whether a briefer treatment interval would be efficacious has not been studied. METHODS/DESIGN: Eligible and consenting women will be randomly assigned to one of two treatments (one cycle of a GnRH agonist or two cycles of a GnRH agonist) prior to IVF/ICSI using a table of random numbers. The primary outcome of this trial is clinical pregnancy rate. Other outcomes include gonadotrophin (Gn) duration, the total dose of follicle-stimulating hormone (FSH) used, number of oocytes retrieved, number of embryos available for transfer, implantation rate, the abortion rate, live birth rate, and incidence of moderate-to-severe ovarian hyperstimulation. The sample size of this trial is estimated to be 421 participants for each of the two arms. Appropriate interim analyses will be conducted by a data monitoring and ethics committee (DMEC), and the final test will be an intention-to-treat analysis. TRIAL REGISTRATION: This trial has been assigned the following registry number: NCT03006406 .

Influence of endometrial thickness on treatment outcomes following in vitro fertilization/intracytoplasmic sperm injection.

BACKGROUND: The study was designed to investigate the roles of endometrial thickness (EMT) at the day of human chorionic gonadotropin (hCG) administration on pregnancy outcomes in a large patient population. METHODS: This retrospective cohort study included 9,952 patients undergoing their first IVF/ICSI with autologous oocytes from January 2011 to January 2015. Patients were divided into three groups based on the EMT (group A:≤8 mm; group B: 9-14 mm and group C:≥15 mm). Live birth rate (LBR), clinical pregnancy rate (CPR), early miscarriage rate (EMR), and ectopic pregnancy rate (EPR) were analyzed. Additionally, the live birth rate was analyzed for patients with single or double gestational sacs. RESULTS: Significant differences (p < 0.05) were detected in the LBRs (30.38%, 45.73% and 54.55% for groups A, B, and C, respectively), CPRs (38.57%, 55.04% and 64.32%, respectively), and EPRs (5.58%, 3.48% and 2.19%, respectively), with thicker endometrial thickness favoring all three parameters. However, no differences were found in the EMRs among the three groups (15.64%, 13.44% and 13.05%, respectively, p > 0.05). After adjusting for female age, body mass index (BMI) and endometrial pattern, the multivariate logistic regression analysis demonstrated that the associations between EMT and LBR (adjusted OR: 2.645; 95% CI 2.020-3.464; p < 0.01), CPR (adjusted OR 2.693 95% CI 2.012-3.605 p < 0.01), and EPR (adjusted OR: 0.298 95% CI 0.101-0.713; p < 0.05) were significant. Additionally, live birth rates in the double gestational sac group were different (p < 0.05) among patients with different EMT (72.73%, 87.28%, and 87.36%, respectively), whereas no difference was found in the single gestational sac group. In the double gestational sac group, LBR was positively correlated with increasing endometrial thickness only in patients with twin pregnancies but not in patients with singletons. CONCLUSIONS: Our study shows that endometrial thickness at the day of hCG administration has an effect on LBR, CPR and EPR, with all three parameters increasing with the EMT. Furthermore, successful twin pregnancies are associated with a thicker endometrium.

Endometrial thickness significantly affects clinical pregnancy and live birth rates in frozen-thawed embryo transfer cycles.

In order to explore the relationship between endometrial thickness on the day of embryo transfer and pregnancy outcomes in frozen-thawed embryo transfer (FET) cycles, we retrospectively analyzed data from 2997 patients undergoing their first FET cycles from January 2010 to December 2012. All patients were divided into three groups (Group A, ≤8 mm; Group B, 9-13 mm; Group C, ≥14 mm) according to the endometrial thickness on embryo transfer day. Compared with patients in the other two groups, patients with thin endometrial thickness in Group A had significantly lower clinical pregnancy rate (33.4%, 41.3% and 45.4%, p < 0.01) and live birth rate (23.8%, 32.2% and 34.0%, p < 0.01). After adjusting for age, body mass index (BMI), baseline follicle stimulating hormone (FSH) FET protocol and number of embryos transferred, the associations between medium endometrial thickness (Group B) and clinical pregnancy rate [adjusted odds ratio (aOR): 1.39; 95% confidence interval (CI): 1.10-1.77, p < 0.01] and live birth rate (aOR: 1.50; 95% CI: 1.16-1.95, p < 0.01) were significant. We conclude that for patients undergoing FET, endometrial thickness on the embryo transfer day significantly affects IVF outcomes in cleavage embryo transfer cycles independent of other factors.

Regulation of endometrial receptivity by the highly expressed HOXA9, HOXA11 and HOXD10 HOX-class homeobox genes.

STUDY QUESTION: Are other HOX genes, in addition to HOXA10, involved in endometrial receptivity? SUMMARY ANSWER: The highly expressed HOXA9, HOXA11 and HOXD10 genes also appear to be involved in endometrial receptivity. WHAT IS KNOWN ALREADY: Within the HOX family of homeobox transcription factor genes are the leading candidates for the regulation of embryonic implantation. A crucial role of HOXA10 in endometrial receptivity has been well established. STUDY DESIGN, SIZE, DURATION: To identify HOX candidate genes, we performed data mining on all 39 human HOX genes in the 'Human body index' gene expression database of normal human tissue. The temporal and spatial expression pattern of four highly expressed HOX genes in the human endometrium was determined. To further investigate the function of these Hox genes, we used a robust in vivo mouse model in which we blocked maternal Hox gene expression. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Analysis of a gene expression profile set in the public domain consisting of 504 samples representing 95 different normal human tissues, showed that in addition to HOXA10, also HOXA9, HOXA11, HOXB6 and HOXD10 mRNA showed increased expression in the human endometrium (16 samples). The temporal and spatial expression pattern of these four HOX genes throughout the menstrual cycle was determined in the endometrium from 27 female patients eligible for IVF-embryo transfer with a normal cycle by quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry. The role of maternal Hoxa9, Hoxa11 and Hoxd10 was assessed in a mouse implantation model by expression knockdown using RNA interference. Forty mice were transfected with Hoxa9-, Hoxa11- or Hoxd10-specific small hairpin RNA (shRNA) constructs or a vector control by injection into the uterine horn at Day 2 after vaginal plug detection (Day 1) (160 mice in total). The effects were examined by qRT-PCR and western blot at Day 4 and litter sizes counted at Day 9 of pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE: HOXA10, HOXA9, HOXA11 and HOXD10 all showed increased expression during the mid-secretory phase of the menstrual cycle (P < 0.01). Knockdown of Hoxa9, Hoxa11 and Hoxd10 in the murine uterus resulted in significantly reduced average implantation rates (P < 0.01) and, with regard to four Hox target genes, also correlated with a significantly increased empty spiracles homolog 2 (Emx2) and insulin-like growth factor binding protein-1 (Igfbp1), and decreased integrin ß3 (Itgb3) and leukemia inhibitory factor (Lif), expression (P < 0.01). LIMITATIONS, REASONS FOR CAUTION: Menstrual cycle stage was not confirmed by serum hormone analysis. We verified the absence of significant differences in stage-specific expression of the reference genes used in our study (ACTB/Actb and GAPDH/Gapdh) and therefore possible limitations of this approach were minimized. In addition, the translatability of our data from a mouse model to patients needs to be investigated further. WIDER IMPLICATIONS OF THE FINDINGS: We provide evidence that three other HOX genes in addition to HOXA10 are involved in endometrial receptivity, and that part of their function is asserted through several known HOX target genes, suggesting the presence of a central HOX signal transduction pathway.

Recombinant luteinizing hormone supplementation in women undergoing in vitro fertilization/ intracytoplasmic sperm injection with gonadotropin releasing hormone antagonist protocol: a systematic review and meta-analysis.

The objective of this meta-analysis is to assess the impact of LH supplementation in women undergoing in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) with gonadotropin releasing hormone (GnRH) antagonist protocol. No significant difference in outcomes between LH supplementation and r-FSH alone in women undergoing IVF/ICSI with GnRH antagonist protocol is currently present, and further studies are necessary for more solid conclusions on pregnancy likelihood to be drawn.

Elevated sperm DNA fragmentation is correlated with an increased chromosomal aneuploidy rate of miscarried conceptus in women of advanced age undergoing fresh embryo transfer cycle.

Background: Male sperm DNA fragmentation (SDF) may be associated with assisted reproductive technology (ART) outcomes, but the impact of SDF on the occurrence of aneuploid-related miscarriage remains controversial. Methods: Genome-wide single-nucleotide polymorphism-based chromosomal microarray analysis was performed on 495 miscarried chorionic villus samples undergone IVF/ICSI treatment from the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University. SDF was assessed using sperm chromatin structure assay. Patients were divided into four groups according to embryo transfer cycle type and maternal age, and the correlation between SDF and chromosome aberration was analyzed. A receiver operating characteristic (ROC) curve was utilized to find the optimal threshold. Results: Total chromosomal aneuploidy rate was 54.95%, and trisomy was the most common abnormality (71.32%). The chromosomally abnormal group had higher SDF than the normal group (11.42% [6.82%, 16.54%] vs. 12.95% [9.61%, 20.58%], P = 0.032). After grouping, elevated SDF was significantly correlated with an increasing chromosome aneuploidy rate only in women of advanced age who underwent fresh embryo transfer (adjusted odds ratio:1.14 [1.00-1.29], adjusted-P = 0.045). The receiver operating characteristic curve showed that SDF can predict the occurrence of chromosomal abnormality of miscarried conceptus in this group ((area under the curve = 0.76 [0.60-0.91], P = 0.005), and 8.5% was the optimum threshold. When SDF was ≥ 8.5%, the risk of such patients increased by 5.76 times (adjusted odds ratio: 6.76 [1.20-37.99], adjusted-P = 0.030). Conclusion: For women of advanced maternal age undergoing fresh embryo transfer, older oocytes fertilized using sperm with high SDF in IVF/ICSI treatment might increase the risk of chromosomal abnormality in miscarried conceptus.

Comparison of clinical outcomes and perinatal outcomes between natural cycle and hormone replacement therapy of frozen-thawed embryo transfer in patients with regular menstruation: a propensity score-matched analysis.

Purpose: To investigate potential differences in pregnancy outcomes among patients with regular menstruation who underwent frozen-thawed embryo transfer using natural cycle (NC) or hormone replacement therapy (HRT). Methods: This study retrospectively analyzed 2672 patients with regular menstruation who underwent FET from November 2015 to June 2021 at the single reproductive medical center. A one-to-one match was performed applying a 0.02 caliper with propensity score matching. Independent factors influencing the live birth and clinical pregnancy rates were screened and developed in the nomogram by logistic regression analysis. The efficacy of live birth rate and clinical pregnancy rate prediction models was assessed with the area under the ROC curve, and the live birth rate prediction model was internally validated within the bootstrap method. Results: The NC protocol outperformed the HRT protocol in terms of clinical pregnancy and live birth rates. The stratified analysis revealed consistently higher live birth and clinical pregnancy rates with the NC protocol across different variable strata compared to the HRT protocol. However, compared to the HRT treatment, perinatal outcomes indicated that the NC protocol was related to a higher probability of gestational diabetes. Multifactorial logistic regression analysis demonstrated independent risk factors for live birth rate and clinical pregnancy rate. To predict the two rates, nomogram prediction models were constructed based on these influencing factors. The receiver operating characteristic curve demonstrated moderate predictive ability with an area under curve (AUC) of 0.646 and 0.656 respectively. The internal validation of the model for live birth rate yielded an average AUC of 0.646 implying the stability of the nomogram model. Conclusion: This study highlighted that NC yielded higher live birth and clinical pregnancy rates in comparison to HRT in women with regular menstruation who achieved successful pregnancies through frozen-thawed embryo transfer. However, it might incur a higher risk of developing gestational diabetes.