Cumulative Live Birth Rate Research Articles

Prevalence of FSH-R Asn680Ser and Ala307Thr receptor polymorphism and their correlation with ART outcomes among infertile Indian-Asian women-a prospective cohort study.

The present prospective cohort study evaluated the prevalence of FSH-R receptor Asn680Ser and Ala307Thr among infertile Indian women and the correlation of these polymorphisms with ART outcomes. Total 804 infertile and 209 fertile controls were enrolled for FSH-R analysis. Correlation of different genotypes with ovarian reserve markers, IVF parameters, and cumulative live birth rates (CLBR) was done among women undergoing IVF. In fertile controls, at 680 position GG (Ser/Ser) was the most common genotype; but among infertile women, all the genotypes were equally distributed. There was no significant difference in ovarian response parameters, oocyte yield, and CLBR among the three genotype groups. Empty follicle syndrome (EFS) was highest in women with AA or AG type at both positions. On categorisation of unexpected poor responders according to POSEIDON stratification; GG genotype at both positions had the lowest risk ratio of low-oocyte yield in ART cycles, but these differences were not statistically significant. This is the largest study from Indian ethnicity showing GG (Ser/Ser) genotype is most common among fertile women. The effect of FSH-R genotypes is very marginal on IVF parameters and is not reflected in CLBR. More prospective data may be required on the correlation of these genotypes with genuine EFS, thus stratifying the next cycles with self or donor oocytes. Routine genetic testing of FSH-R polymorphism should not be done except in a research setting. As both 680 and 307 positions are in linkage disequilibrium, only 680 position analysis may be done in a research setting.

Effect of medroxyprogesterone acetate dose in progestin-primed ovarian stimulation on pregnancy outcomes in poor ovarian response patients with different body mass index levels.

For the poor ovarian response (POR) population, the relationship between medroxyprogesterone acetate (MPA) dose in progestin-primed ovarian stimulation (PPOS) and clinical outcome is still unclear. This study aims to explore the effect of MPA dose in PPOS on clinical outcomes in POSEIDON group 3 and 4 patients with different body mass index (BMI) levels, hoping to provide clinical doctors with better options for controlled ovarian hyperstimulation (COH) programs. This is a retrospective analysis of 253 oocyte retrieval cycles of POSEIDON group 3 and 4 patients who underwent PPOS protocol in IVF/ICSI treatment at the Reproductive Medical Center of Renmin Hospital of Wuhan University from March 2019 to April 2022. The effects of different MPA doses (8 mg/d or 10 mg/d) on pregnancy outcomes were compared in normal BMI (18.5-24 kg/m2) and high BMI (≥24 kg/m2) patients, and multivariate logistic regression analysis was performed to analyze the factors affecting pregnancy outcomes. For normal BMI patients, the 8-mg/d MPA group had a higher embryo implantation rate (33.78% vs. 18.97%, P = 0.012). For high BMI patients, the 10-mg/d MPA group had a higher HCG positive rate (55.00% vs. 25.00%, P = 0.028), clinical pregnancy rate (50.00% vs. 20.00%, P = 0.025), and cumulative pregnancy rate (37.74% vs. 13.79%, P = 0.023) compared with the 8-mg/d MPA group. There was no significant difference in cumulative live birth rate between the 8-mg/d and 10-mg/d MPA groups in patients with normal or high BMI. The results of multivariate logistic regression showed a significant correlation between MPA dose and cumulative pregnancy in the high BMI population (OR = 0.199, 95% CI: 0.046~0.861, P = 0.031). For POR patients with high BMI, 10 mg/d of MPA in the PPOS protocol had a higher cumulative pregnancy rate than 8 mg/d of MPA, but it had no significant effect on the cumulative live birth rate.

Preimplantation genetic testing for aneuploidy could not improve cumulative live birth rate among 1003 couples with recurrent pregnancy loss.

Preimplantation genetic testing for aneuploidy could not improve cumulative live birth rate among 1003 couples with recurrent pregnancy loss.

Cumulative live birth rates following intrauterine insemination using donor and husband sperm in different age groups: Acohort study of 10 415 insemination cycles.

To assess the age-specific cumulative live birth rates (CLBRs) in intrauterine insemination (IUI) cycles using either donor or husband sperm, and to investigate the impact of sperm sources on IUI success among women within the same age group. This retrospective cohort study comprised women who underwent IUI with donor sperm (IUI-D) or husband sperm (IUI-H) from 2017 to 2021. The women were stratified based on their age at the initiation of insemination into four categories: <35, 35-37, 38-39 and ≥40 years. A total of 5253 women undergoing 10 415 insemination cycles (3354 with IUI-D and 7061 with IUI-H) were included. The CLBRs decreased significantly with increasing maternal age within donor and husband insemination groups (P < 0.001). In the IUI-D group, the crude CLBRs were 61.50% in women aged <35, 48.91% in 35-37, 24.14% in 38-39 and 11.76% in the ≥40-year age category, respectively. The corresponding rates in the IUI-H group were 27.62%, 22.96%, 13.73% and 6.90%, respectively. Within the <35 and 35-37-year age categories, the CLBRs were significantly higher following IUI-D cycles compared to IUI-H cycles, with hazard ratios (HR) of 1.85 (1.68-2.04) and 1.69 (1.16-2.47), respectively. However, within the 38-39 and ≥40-year age categories, both IUI-D and IUI-H resulted in comparable low CLBRs, with HRs of 1.91 (0.77-4.76) and 1.80 (0.33-9.86), respectively. Advanced maternal age affects the whole process of fertility. Therefore, it could be reasonable to limit the number of IUI performed in women aged 40 years and older, even in couple using donor sperm for reproduction.

Impact of dehydroepiandrosterone sulfate and free androgen index on pregnancy and neonatal outcomes in PCOS patients

BackgroundPolycystic ovary syndrome (PCOS) is a prevalent endocrine disorder associated with infertility and pregnancy complications. The pathogenesis of PCOS and its impact on reproductive function may be influenced by the source of androgens, including testosterone, free androgen, dehydroepiandrosterone sulfate (DHEAS). However, the differential effects of these androgen on pregnancy and neonatal outcomes and the cut-off value of East Asian population with PCOS remain unclear.MethodsA retrospective cohort study was conducted at the Reproductive Medicine Center of the First Affiliated Hospital of Sun Yat-sen University from January 2015 to November 2022, involving 636 cycles of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Subgroup analyses were performed using cut-off values of 6.4 for free androgen index (FAI), 9.5 µmol/L for DHEAS. Pregnancy and neonatal outcomes were compared between groups. Restricted cubic spline (RCS) was used to identify significant cut-off values affecting pregnancy.ResultsHigher FAI levels (> 6.4) were associated with decrease in clinical pregnancy rate (PR) (50.61% vs. 41.66%, p = 0.024), live birth rate (LBR) (42.42% vs. 32.35%, p = 0.011). When DHEAS levels exceeded 9.5 µmol/L, there was a significant decrease in clinical PR (51.27% vs. 42.73%, P = 0.039), LBR (42.73% vs. 32.73%, P = 0.012). Negative correlations were also observed between DHEAS levels and cumulative pregnancy rate (70.57% vs 56.62% p = 0.002) and cumulative live birth rate (CLBR) (59.35% vs 43.37%, p = 0.0007). Both FAI and DHEAS elevated is associated with the lowest clinical pregnancy rate (37.84%). Conversely, when solely FAI is elevated, the pregnancy rate increases to 52.38%, while an elevation in DHEAS alone is associated with a pregnancy rate of, both of which are lower than when neither FAI nor DHEAS are elevated (60.68%). The live birth rates exhibit a similar trend (30.00% vs 40.00% vs 41.83% vs 44.48%). RCS revealed a significant decrease in CPR and CLBR when DHEA levels exceeded 7.69 umol/L, while the cut-off value of FAI was 6.36 for CPR and CLBR.ConclusionIn conclusion, PCOS patients with biochemical hyperandrogenism show unsatisfactory clinical PR and CLBR when undergoing assisted reproductive technology (ART). This may be attributed to the influence of both adrenal-derived DHEAS and ovarian-derived FAI on the unfavorable pregnancy outcomes.

Acrosin activity negatively influences the cumulative live birth rate in patients undergoing IVF treatment

Research questionIs acrosin activity related to cumulative live birth rate (CLBR) over 1 year after IVF, intracytoplasmic sperm injection (ICSI) treatment or both? DesignRetrospective monocentric cohort study of 5704 couples who started IVF/ICSI treatments between 2016 and 2021. Acrosin activity was determined by a modified Kennedy method using a commercial kit. Patients were divided into two groups according to their acrosin activity: below 25 μIU/106 spermatozoa; and an acrosin activity 25 μIU/106 spermatozoa or above. Primary outcome was the CLBR, defined as an ongoing pregnancy leading to live birth that had arisen from all embryo transfers carried out within 1 year after the first ovum retrieval. Both conservative and optimistic methods were used for estimating CLBRs. ResultsThe CLBRs of patients with an acrosin activity below 25 μIU/106 spermatozoa were found to be significantly lower than those of patients with an acrosin activity 25 μIU/106 spermatozoa or above by conservative (48.5% versus 55.4%, P = 0.02) and optimistic (63.7% versus 70.3%, P = 0.047) methods after adjusting for confounders. When acrosin activity was regarded as a continuous variable, significant negative relationships between acrosin activity and CLBR were identified in subgroups: young couples (men and women aged younger than 30 years) and couples from whom no more than 10 eggs were retrieved. ConclusionLow acrosin activity levels were correlated with decreasing CLBRs over 1 year. These findings suggest that acrosin activity can be used as a predictor for CLBRs before starting IVF/ICSI treatment to enhance the effectiveness of counselling.

Age-related increase in live-birth rates of first frozen thaw embryo versus first fresh transfer in initial assisted reproductive technology cycles without PGT

BackgroundThe landscape of assisted reproductive technology (ART) has seen a significant shift towards frozen-thawed embryo transfers (FET) over fresh transfers, driven by technological advancements and clinical considerations. This study aimed to compare live birth outcomes between primary FET and fresh transfers, focusing on cycles without preimplantation genetic testing (PGT), using United States national data from the SART CORS database spanning from 2014 to 2020.MethodsWe performed a retrospective cohort study of autologous first ART cycles without PGT comparing primary embryo transfer (frozen thaw vs. fresh) success rates from the 2014–2020 SARTCORS database. Live-birth rates (LBR) and cumulative live-birth rates (CLBR) were compared between first FET versus first fresh embryo transfer from an index retrieval. Multivariate logistic regression (MLR) determined association between live birth outcomes and method of transfer. In a subsequent sub-analysis, we compared these two embryo transfer methods among patients with either diminished ovarian reserve (DOR) or male factor infertility.Results228,171 first ART cycles resulted in primary embryo transfer. 62,100 initial FETs and 166,071 fresh transfers were compared. Initial FETs demonstrated higher LBR and CLBR compared to fresh transfers (LBR 48.3% vs. 39.8%, p < 0.001; CLBR 74.0% vs. 60.0%, p < 0.0001). MLR indicated greater chances of live birth with FET across all age groups, with adjusted odds ratio (aOR) of live-birth incrementally increasing with advancing age groups. For DOR cycles, LBR and CLBR were significantly higher for FET compared to fresh (33.9% vs. 26.0%, p < 0.001, 44.5% vs. 37.6%, p < 0.0001), respectively. MF cycles also demonstrated higher LBR and CLBR with FET (52.3% vs. 44.2%, p < 0.001, 81.2% vs. 68.9%, p < 0.0001), respectively. MLR demonstrated that in DOR cycles, initial FET was associated with greater chance of live birth in age groups ≥ 35yo (p < 0.01), with aOR of live birth increasingly considerably for those > 42yo (aOR 2.63, p < 0.0001).ConclusionsOverall LBR and CLBR were greater for first FET than fresh transfers with incremental increases in odds of live birth with advancing age, suggesting the presence of a more favorable age-related change in endometrial receptivity present in frozen-thawed cycles. For both DOR and MF cycles, LBR and CLBR after primary transfer were greater for first FET than fresh. However, this was particularly evident in older ages for DOR cycles. This suggests that supraphysiologic stimulation in older DOR cycles may be detrimental to endometrial receptivity, which is in part corrected for in FET cycles.

The (cost-) effectiveness Of Surgical excision of Colorectal endometriosis compared to ART treatment trAjectory (TOSCA study) - a study protocol.

Currently, the optimal treatment to increase the chance of pregnancy and live birth in patients with colorectal endometriosis and subfertility is unknown. Evidence suggests that that both surgery and in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) are effective in improving live birth rate (LBR) among these women. However, the available evidence is of low quality, reports highly heterogeneous results, lacks direct comparison between both treatment options and does not assess whether a combination strategy results in a higher LBR compared to IVF/ICSI-only treatment. Additionally, the optimal timing of surgery within the treatment trajectory remains unclear. The primary objective of the TOSCA study is to assess the effectiveness of surgical treatment (potentially combined with IVF/ICSI) compared to IVF/ICSI-only treatment to increase the chance of an ongoing pregnancy resulting in a live birth in patients with colorectal endometriosis and subfertility, measured by cumulative LBR. Secondary objectives are to assess and compare quality of life and cost-effectiveness in both groups. Patients will be followed for 40 months after inclusion or until live birth. The TOSCA study is expected to be completed in 6 years.

Excessive Exogenous Gonadotropins and Genetic and Pregnancy Outcomes After Euploidy Embryo Transfer

The safety of exogenous gonadotropin treatment, based on its effect on embryos and pregnancy outcomes, remains inconclusive. To evaluate the associations of different doses and durations of gonadotropins with embryonic genetic status and pregnancy outcomes after euploid embryo transfer in couples with infertility. This study was a post hoc analysis of a multicenter randomized clinical trial (RCT) conducted at 14 reproductive centers throughout China from July 2017 to June 2018 that evaluated the cumulative live birth rate with or without preimplantation genetic testing for aneuploidy (PGT-A) among couples with infertility and good prognosis. The PGT-A group from the original RCT was selected for secondary analysis. Patients were divided into 4 groups according to the total dosage of exogenous gonadotropins and treatment duration: group 1 (≤1500 IU and <10 days), group 2 (≤1500 IU and ≥10 days), group 3 (>1500 IU and <10 days), and group 4 (>1 500 IU and ≥10 days). Group 1 served as the control group. Data were analyzed from June through August 2023. Blastocyst biopsy and PGT-A. The primary outcomes were embryonic aneuploidy, embryonic mosaicism, and cumulative live birth rates after euploid embryo transfer. A total of 603 couples (mean [SD] age of prospective mothers, 29.13 [3.61] years) who underwent PGT-A were included, and 1809 embryos were screened using next-generation sequencing. The embryo mosaicism rate was significantly higher in groups 2 (44 of 339 embryos [13.0%]; adjusted odds ratio [aOR], 1.69 [95% CI, 1.09-2.64]), 3 (27 of 186 embryos [14.5%]; aOR, 1.98 [95% CI, 1.15-3.40]), and 4 (82 of 651 embryos [12.6%]; aOR, 1.60 [95% CI, 1.07-2.38]) than in group 1 (56 of 633 embryos [8.8%]). There were no associations between gonadotropin dosage or duration and the embryo aneuploidy rate. The cumulative live birth rate was significantly lower in groups 2 (83 of 113 couples [73.5%]; aOR, 0.49 [95% CI, 0.27-0.88]), 3 (42 of 62 couples [67.7%]; aOR, 0.41 [95% CI, 0.21-0.82]), and 4 (161 of 217 couples [74.2%]; aOR, 0.53 [95% CI, 0.31-0.89]) than in group 1 (180 of 211 couples [85.3%]). In this study, excessive exogenous gonadotropin administration was associated with increased embryonic mosaicism and decreased cumulative live birth rate after euploid embryo transfer in couples with a good prognosis. These findings suggest that consideration should be given to minimizing exogenous gonadotropin dosage and limiting treatment duration to improve embryo outcomes and increase the live birth rate. ClinicalTrials.gov Identifier: NCT03118141.

Reproductive outcomes of dual trigger therapy with GnRH agonist and hCG versus hCG trigger in women with diminished ovarian reserve: a retrospective study

BackgroundDiminished ovarian reserve (DOR) is one of the obstacles affecting the reproductive outcomes of patients receiving assisted reproductive therapy. The purpose of this study was to investigate whether dual trigger, including gonadotropin‐releasing hormone agonist (GnRHa) and human chorionic gonadotropin (hCG), can improve pregnancy outcomes in patients with DOR undergoing in vitro fertilization (IVF) cycles using mild stimulation protocols.MethodsA total of 734 patients with DOR were included in this retrospective study. Patients were divided into a recombinant hCG trigger group and a dual trigger group (hCG combined with GnRHa) according to the different trigger drugs used. The main outcome measures included the number of oocytes retrieved, the fertilization rate, the number of transferable embryos, the implantation rate, the clinical pregnancy rate, the miscarriage rate, the live birth rate (LBR), and the cumulative live birth rate (CLBR). Generalized linear model and logistic regression analyses were performed for confounding factors.ResultsThere were 337 cycles with a single hCG trigger and 397 cycles with dual trigger. The dual trigger group demonstrated significantly higher numbers of retrieved oocytes [3.60 vs. 2.39, adjusted β = 0.538 (0.221–0.855)], fertilized oocytes [2.55 vs. 1.94, adjusted β = 0.277 (0.031–0.523)] and transferable embryos [1.22 vs. 0.95, adjusted β = 0.162 (-0.005–0.329)] than did the hCG trigger group, whereas no significant difference in the fertilization rate was observed between the two groups. Moreover, the embryo transfer cancellation rate (35.5% vs. 43.9%) was obviously lower in the dual trigger group. Among the fresh embryo transfer cycles, the implantation rate, clinical pregnancy rate, miscarriage rate and live birth rate were similar between the two groups. After controlling for potential confounding variables, the trigger method was identified as an independent factor affecting the number of oocytes retrieved but had no significant impact on the CLBR.ConclusionsDual triggering of final oocyte maturation with hCG combined with GnRHa can significantly increase the number of oocytes retrieved in patients with DOR but has no improvement effect on the implantation rate, clinical pregnancy rate or LBR of fresh cycles or on the CLBR.

Impact of thyroid autoimmunity on the cumulative live birth rates after IVF/ICSI treatment cycles

BackgroundCumulative live birth rate (CLBR) is considered as the most important endpoint for assessing the probability of having a baby in a complete in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment cycle. Many previous studies have focused on the association between thyroid autoimmunity (TAI) and live birth rate after first embryo transfer cycle, however, evidence on whether the presence of TAI affects the CLBR is lacking. The purpose of this study is to investigate the impact of TAI on the CLBR in a complete IVF/ICSI cycle.MethodsThis retrospective study included 12,796 women who underwent their first IVF/ICSI treatment between January 2019 and February 2021. Based on the levels of thyroid antibodies, 2,603 women were assigned to the TAI group, and 10,193 women were assigned to the control group. Subgroup analysis was performed according to the different causes of infertility (including male factor only, ovulation disorder, tubal factor, endometriosis and unexplained infertility) and different types and titres of thyroid antibodies. The primary outcome in this study was CLBR, which included live births from the fresh embryo transfer cycle and all subsequent frozen-thawed embryo transfer cycles performed before December 2021.ResultsThere was no significant difference in the CLBR between the TAI and control groups, even after adjusting for relevant confounders including age, body mass index, cause of infertility, thyroid function, protocols of controlled ovarian stimulation, type of transfer (fresh vs. frozen), type of transferred embryo (cleavage-stage embryo vs. blastocyst), and fertilization method (IVF vs. ICSI) (cumulative live birth: 50.6% vs. 52.1%, OR 0.94, 95% CI 0.86–1.02, adjusted OR 0.97, 95%CI 0.89–1.06). Subgroup analysis showed that no significant difference was observed in CLBR between the TAI and control groups for all causes of infertility, except for infertility attributed to endometriosis. Among women with endometriosis, the CLBR was significantly lower in the TAI group than that in the control group; however, this difference was not significant after adjusting for potential confounders including age, body mass index, thyroid function, protocols of controlled ovarian stimulation, type of transfer (fresh vs. frozen), type of transferred embryo (cleavage-stage embryo vs. blastocyst), and fertilization method (IVF vs. ICSI) (cumulative live births: 43.1% vs. 51.0%, OR 0.73, 95% CI 0.53–0.99, adjusted OR 0.74, 95% CI 0.53–1.02). Another subgroup analysis demonstrated that the type and titre of thyroid antibody did not affect CLBR in women with TAI.ConclusionsIn our study, there was no significant difference in the CLBR between women with TAI and those without TAI, which suggests that TAI did not affect the chances of having a baby in a complete IVF/ICSI treatment cycle.

Reducing radicality in fertility-sparing surgery is associated with improved in vitro fertilization outcome in early-stage cervical cancer: A national retrospective study

ObjectiveFertility-sparing surgery (FSS) aims to achieve oncological outcomes that are non-inferior to radical treatment while preserving fertility and optimizing reproductive results. This study assesses in vitro fertilization (IVF) outcomes in early-stage cervical cancer survivors following FSS, comparing radical and non-radical approaches. MethodsThis retrospective analysis used data from Hungary's National Health Insurance Fund (2004–2022) on patients who underwent IVF treatment following FSS for early-stage cervical cancer at ten Hungarian fertility clinics. Patients were classified into radical and non-radical surgical groups, with the uterine arteries being spared in the non-radical procedures. RStudio (R software version: 4.2.2) was used for statistical analysis. Student's t-test was used to compare group means, and Fisher's exact test was applied to assess independence and distributions between categorical variables, and to estimate odds. ResultsThe study analyzed data from 122 IVF treatment cycles involving 36 patients. The non-radical group had a significantly higher live birth rate (83%, 5/6 compared to the radical group (17%, 5/30). Additionally, the non-radical group had a significantly higher implantation rate and cumulative live birth rate per oocyte retrieval (37%, 7/19 and 55%, 6/11 respectively) compared to the radical group (8%, 12/148 and 6%, 5/80 respectively). ConclusionThis is the largest study to evaluate IVF outcomes in young cervical cancer survivors who have undergone FSS. The findings suggest that less radical procedures are associated with significantly better IVF outcomes. These results emphasize the importance of considering oncological safety and reproductive outcomes together when choosing FSS for early-stage cervical cancer patients. It also highlights the reproductive benefits of performing less radical surgery.

Comparison of pregnancy outcomes in women with normal ovarian response to the gonadotropin-releasing hormone agonist protocol using different trigger methods: a single-center retrospective cohort study based on propensity score matching.

To investigate whether gonadotropin-releasing hormone agonist (GnRH-a) combined with human chorionic gonadotropin (HCG) can improve pregnancy outcomes in patients with normal ovarian response (NOR). In this retrospective cohort study, data of 404 NOR patients undergoing fresh embryo transfer (ET) from 2018 to 2022 were studied. Patients were divided into HCG group and HCG plus GnRH-a group according to trigger methods. After confounding factors were controlled by propensity score matching, 67 cases were included in HCG group and HCG plus GnRH-a group, respectively, and pregnancy outcomes were assessed. Basal data, ovarian stimulation, embryological data and pregnancy outcomes were compared. The effect of trigger methods on pregnancy outcomes was analyzed by binary logistic regression. There was no statistically significant differences in embryological data, embryo implantation rate, clinical pregnancy rate, live birth rate of ET, number of fresh embryos transferred and total number of embryos transferred after one cycle of oocyte retrieval. While, cumulative live birth rate (CLBR) was better in the dual-trigger group than in the HCG group. The binary logistic regression analysis indicated that the trigger methods had an independent influence on embryo implantation and cumulative live birth. During IVF/ICSI, dual-trigger could potentially play a role in improving oocyte quality, ensuring embryo implantation rate, clinical pregnancy rate, live birth rate of ET and cumulative live birth rate at the end of one ovum pick-up (OPU) cycle, and reducing the physical, temporal and financial negative consequences due to repeated OPU cycle.

Association between body mass index and in vitro fertilization/intra-cytoplasmic sperm injection outcomes: An analysis of 15,124 normal ovarian responders in China.

High body mass index (BMI) results in decreased fecundity, and women with high BMI have reduced rates of clinical pregnancy and live birth in in vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI). Meanwhile, ovarian responses show great heterogeneity in patients with a high BMI. This study aimed to analyze the effects of a high BMI on IVF/ICSI outcomes in the Chinese female with normal ovarian response. We performed a retrospective cohort study comprising 15,124 patients from the medical record system of the Reproductive Center of Peking University Third Hospital, with 3530 (23.3%) in the overweight group and 1380 (9.1%) in the obese group, who had a normal ovarian response (5-15 oocytes retrieved) and underwent fresh embryo transfer (ET) cycles from January 2017 to December 2018, followed by linked frozen-thawed embryo transfer (FET) cycles from January 2017 to December 2020. Cumulative live birth rate (CLBR) was used as the primary outcome. Furthermore, a generalized additive model was applied to visually illustrate the curvilinear relationship between BMI and the outcomes. We used a decision tree to identify the specific population where high BMI had the greatest effect on IVF/ICSI outcomes. High BMI was associated with poor IVF/ICSI outcomes, both in cumulative cycles and in separate fresh ET or FET cycles. In cumulative cycles, compared with the normal weight group, obesity was correlated with a lower positive pregnancy test rate (adjusted odds ratio [aOR]: 0.809, 95% confidence interval [CI]: 0.682-0.960), lower clinical pregnancy rate (aOR: 0.766, 95% CI: 0.646-0.907), lower live birth rate (aOR: 0.706, 95% CI: 0.595-0.838), higher cesarean section rate (aOR: 2.066, 95% CI: 1.533-2.785), and higher rate of large for gestational age (aOR: 2.273, 95% CI: 1.547-3.341). In the generalized additive model, we found that CLBR declined with increasing BMI, with 24kg/m 2 as an inflection point. In the decision tree, BMI only made a difference in the population aged ≤34.5years, with anti-Mullerian hormone >1.395ng/mL, and the first time for IVF. High BMI was related to poor IVF/ICSI outcomes in women with a normal ovarian response, and CLBR declined with increasing BMI, partly due to suppressed endometrial receptivity. A high BMI had the most negative effect on young women with anticipated positive prognoses.

Effects of ovarian response prediction index and follicle-oocyte index on pregnancy outcomes: a retrospective cohort study of 12,218 fresh transfer cycles

Objective: To investigate the potential relationships among the ovarian response prediction index (ORPI), follicle-oocyte index (FOI), and clinical pregnancy rate (CPR) in women undergoing their first in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) fresh cycle transfer. Methods: In this retrospective cohort study, we included 12,218 women who underwent their first IVF/ICSI-ET cycle between December 2014 and January 2021. The primary and secondary outcomes of our study were CPR and cumulative live birth rate (CLBR), respectively. The data were divided into three groups according to the ORPI and FOI tertiles. Multivariate logistic regression analyses, stratification analyses, interaction, restricted cubic splines, and receiver operating characteristic (ROC) curves were constructed to identify the relationships among ORPI, FOI, and CPR. Results: A statistically significant increase in CPR was detected from the lowest to the highest tertile group (ORPI: 48.12%, 54.07%, and 53.47%, P &lt;0.001; FOI: 49.99%, 52.95%, and 52.71%, P = 0.012). A higher CLBR was observed in the high group (ORPI: 38.63%, 44.62%, and 44.19%, P &lt;0.001; FOI: 41.02%, 43.78%, and 42.59%, P = 0.039). Multivariate logistic regression analysis revealed no statistically significant differences between ORPI, FOI, and neither CPR (odds ratio [OR] [95% confidence interval {CI}], 0.99 [0.97–1.00] vs. [1.02 {0.84–1.24}]) nor CLBR (OR [95% CI], 0.99 [0.97–1.01] vs. 0.99 [0.81–1.20]). No significant association was found among FOI, ORPI, and CPR, even in the subgroups. Restricted cubic spline analyses indicated the existence of a non-linear relationship across the entire range of FOI and ORPI. The ORPI and FOI variables had poor predictive ability (AUC &lt; 0.60) for CPR. Conclusions: Both ORPI and FOI are not reliable predictors of clinical pregnancy or live birth outcomes in fresh ETs. Clinicians and researchers should avoid using FOI and ORPI to assess pregnancy outcomes after fresh ET because of their limited relevance and predictive value.

Does recurrent implantation failure exist? Prevalence and outcomes of five consecutive euploid blastocyst transfers in 123987 patients.

What are the clinical pregnancy and live birth rates in women who underwent up to two more euploid blastocyst transfers after three failures in the absence of another known factor that affects implantation? The fourth and fifth euploid blastocyst transfers resulted in similar live birth rates of 40% and 53.3%, respectively, culminating in a cumulative live birth rate of 98.1% (95% CI = 96.5-99.6%) after five euploid blastocyst transfers. The first three euploid blastocysts have similar implantation and live birth rates and provide a cumulative live birth rate of 92.6%. An international multi-center retrospective study was conducted at 25 individual clinics. The study period spanned between January 2012 and December 2022. A total of 123987 patients with a total of 64572 euploid blastocyst transfers were screened for inclusion. Patients with a history of any embryo transfer at another clinic, history of any unscreened embryo transfer at participating clinics, parental karyotype abnormalities, the use of donor oocytes or a gestational carrier, untreated intracavitary uterine pathology (e.g. polyp, leiomyoma), congenital uterine anomalies, adenomyosis, communicating hydrosalpinx, endometrial thickness <6 mm prior to initiating of progesterone, use of testicular sperm due to non-obstructive azoospermia in the male partner, transfer of an embryo with a reported intermediate chromosome copy number (i.e. mosaic), preimplantation genetic testing cycles for monogenic disorders, or structural chromosome rearrangements were excluded. Ovarian stimulation protocols and embryology laboratory procedures including trophectoderm biopsy followed the usual practice of each center. The ploidy status of blastocysts was determined with comprehensive chromosome screening. Endometrial preparation protocols followed the usual practice of participating centers and included programmed cycles, natural or modified natural cycles. A total of 105 (0.085% of the total population) patients met the criteria and underwent at least one additional euploid blastocyst transfer after failing to achieve a positive pregnancy test with three consecutive euploid blastocyst transfers. Outcomes of the fourth and fifth euploid blastocyst transfers were similar across participating centers. Overall, the live birth rate was similar with the fourth and fifth euploid blastocysts (40% vs 53.3%, relative risk = 1.33, 95% CI = 0.93-1.9, P value = 0.14). Sensitivity analyses excluding blastocysts biopsied on Day 7 postfertilization, women with a BMI >30 kg/m2, cycles using non-ejaculate or donor sperm, double-embryo transfer cycles, and cycles in which the day of embryo transfer was modified due to endometrial receptivity assay test result yielded similar results. Where data were available, the fourth euploid blastocyst had similar live birth rate with the first one (relative risk = 0.84, 95% CI = 0.58-1.21, P = 0.29). The cumulative live birth rate after five euploid blastocyst transfers was 98.1% (95% CI = 96.5-99.6%). Retrospective design has its own inherent limitations. Patients continuing with a further euploid embryo transfer and patients dropping out from treatment after three failed euploid transfers can be systematically different, perhaps with regard to ovarian reserve or economic status. Implantation failure seems to be mainly due to embryonic factors. Given the stable and high live birth rates up to five euploid blastocysts, unexplained recurrent implantation failure should have a prevalence of <2%. Proceeding with another embryo transfer can be the best next step once a known etiology for implantation failure is ruled out. None. N/A.

Pretreatment with oral contraceptive pills in women with PCOS scheduled for IVF: a randomized clinical trial

Abstract STUDY QUESTION What is the effect of pretreatment with oral contraceptive pills (OCPs) on oocyte and embryo quality and pregnancy rates in women with polycystic ovary syndrome (PCOS) scheduled for IVF/ICSI cycles? SUMMARY ANSWER In women with PCOS who underwent a first or second IVF/ICSI cycle with a GnRH antagonist protocol and were randomized to start ovarian stimulation immediately, the quality of cleavage-stage embryos was non-inferior to pretreatment with OCP. WHAT IS KNOWN ALREADY PCOS in Asian populations is characterized by high levels of circulating LH in the early follicular phase. Previous studies indicated that inappropriately high LH levels might affect oocyte maturation and fertilization rates, and impaired embryo quality, consequently resulting in higher rates of impaired pregnancy and miscarriage in women with PCOS. OCPs are frequently used as pretreatment to lower LH levels in PCOS patients. STUDY DESIGN, SIZE, DURATION We performed a randomized controlled trial. After informed consent, women diagnosed with PCOS scheduled for their first or second IVF/ICSI cycle with a GnRH antagonist protocol were randomized to receive OCPs (OCP group) or start ovarian stimulation immediately, regardless of the day of the menstrual cycle (non-OCP group). Using a non-inferiority hypothesis, the sample size was calculated at 242 women. The study lasted from 7 February 2018 to 31 August 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 242 infertility patients with PCOS undergoing the first or second cycle of IVF or ICSI were enrolled and randomized into two groups. In the OCP group, recombinant FSH was started on Day 7 of the washout period after pretreatment with OCP. In the non-OCP group, recombinant FSH was started immediately regardless of the day of the menstrual cycle. All participants received standardized GnRH antagonist ovarian stimulation. The freeze-all strategy was applied to all participants. The primary outcome was the number of good-quality embryos on Day 3 after insemination. Secondary outcomes included the rates of blastocyst formation, implantation, clinical pregnancy, and live birth from the first frozen/warmed embryo transfer cycles and cumulative live birth rates. MAIN RESULTS AND THE ROLE OF CHANCE We randomized 242 women to receive OCP (n = 121) or start immediately with ovarian stimulation (n = 121). The number of good-quality embryos on Day 3 in the OCP group was non-inferior to the non-OCP group (OCP group versus non-OCP group, 6.58 ± 4.93 versus 7.18 ± 4.39, AD −0.61, 95% CI: −1.86 to 0.65, P = 0.34). The rates of blastocyst formation (55.4% versus 52.9%, relative risk (RR) 1.11, 95% CI: 0.96 to 1.28, P = 0.17), implantation (63.0% versus 65.5%, RR 0.90, 95% CI: 0.53 to 1.53, P = 0.79), clinical pregnancy (67.9% versus 68.8%, RR 0.96, 95% CI: 0.54 to 1.71, P = 1.0), and live birth rate (52.8% versus 55.1%, RR 0.92, 95% CI: 0.53 to 1.56, P = 0.79) of the first frozen/warmed embryo transfer cycles were all comparable between the OCP and non-OCP group, respectively. Cumulative live birth rates were also similar in the OCP and non-OCP groups (78.3% versus 83.5%, respectively RR 0.71, 95% CI: 0.36 to 1.42, P = 0.39). LIMITATIONS, REASONS FOR CAUTION Only patients with PCOS in Southern China were recruited. Therefore, caution is necessary when generalizing our results to all such patients with PCOS. Also, since a freeze-only strategy was used, the results of this study are only applicable when infertile women with PCOS undergo the freeze-only method. The obvious treatment difference between the two groups meant that the study was designed as an open-label study for women and doctors. The study had a randomized controlled design that minimized bias. WIDER IMPLICATIONS OF THE FINDINGS Pretreatment with OCPs to lower LH levels in patients with PCOS before ovarian stimulation in IVF or ICSI cycles may not improve the quality of cleavage-stage embryos. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the National Key Research and Development Program of China (No. 2023YFC2705503). This study was supported in part by the Investigator-Initiated Studies Program (grant from MSD and Organon). BWM reports consultancy, travel support, and research funding from Merck. He reports consultancy from Organon and Norgine, and also reports holding stock from ObsEva. No conflicts of interest are declared for the other authors. TRIAL REGISTRATION NUMBER Chinese Clinical Trial Registry (No. chiCTR1800014822). URL: https://www.chictr.org.cn/showproj.html?proj=25280 TRIAL REGISTRATION DATE 7 February 2018. DATE OF FIRST PATIENT’S ENROLLMENT 22 February 2018.

Do serum vitamin D levels affect assisted reproductive outcomes and perinatal outcomes in young non-PCOS patients? A retrospective study.

This study aimed to determine the influence of serum vitamin D levels on assisted reproductive and perinatal outcomes in young non-polycystic ovary syndrome (PCOS) patients. A total of 3397 non-PCOS women under 35years who underwent their first IVF/ICSI cycle at the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University, from 2018 to 2019, were included. The women were categorized into two groups based on their serum 25(OH)D concentrations: deficient group [25(OH)D < 50nmol/L] and non-deficient group [25(OH)D ≥ 50nmol/L]. Ovulation induction results, clinical pregnancy rate, cumulative live birth rate (CLBR), and perinatal outcomes of both groups were compared. A total of 1113 non-PCOS women had successful pregnancies in their first completed IVF cycle. Comparison of laboratory results between the two groups revealed a significantly higher number of oocytes retrieved in the vitamin D-non-deficient group (15.2 ± 6.8 vs. 14.5 ± 6.7, p = 0.015). After controlling for confounding factors, there was no significant difference in the CLBR between the vitamin D-deficient group and the non-deficient group (71.0%, 1,973/2,778 vs. 69.0%, 427/619, p = 0.314, unadjusted). The prevalence of gestational diabetes mellitus (GDM) was higher in the vitamin D-deficient group than in the vitamin D-non-deficient group in both fresh-cycle singleton live births (3.8% vs. 1.2%) and twin live births (2.3% vs. 1.5%). This study demonstrated that vitamin D-deficient group had a lower number of oocytes retrieved than the non-deficient group and a higher prevalence of GDM, suggesting that vitamin D deficiency impacts assisted pregnancies and perinatal outcomes in infertile non-PCOS women. However, further studies are required to confirm these findings.

A history of recurrent pregnancy loss is associated with increased perinatal complications, but not necessarily a longer birth interval: a population study spanning 18 years.

Is there a difference in the time interval between the first and second live births among individuals with and without recurrent pregnancy loss (RPL)? Primary RPL (two or more pregnancy losses before the first live birth) is associated with a shorter time interval between the first and second live births compared with individuals without RPL, but this association is reversed in patients with secondary RPL (RPL patients with no or one pregnancy loss before the first live birth). There is limited information regarding the ability to have more than one child for patients with RPL. Previous studies have investigated the time to live birth and the live birth rate from the initial presentation to clinical providers. Most of the previous studies have included only patients treated at specialized RPL clinics and thus may be limited by selection bias, including patients with a more severe condition. We conducted a population-based retrospective cohort study of 184241 participants who delivered in British Columbia, Canada, and had at least two recorded live births between 2000 and 2018. The aim was to study the differences in the time interval between the first and second live births and the prevalence of pregnancy complications in patients with and without RPL. Additionally, 198319 individuals with their first live birth between 2000 and 2010 were studied to evaluate cumulative second live birth rates. Among individuals with at least two recorded live births between 2000 and 2018, 12321 patients with RPL and 171920 participants without RPL were included. RPL was defined as at least two pregnancy losses before 20 weeks gestation. Patients with primary RPL had at least two pregnancy losses occurring before the first live birth, while patients with secondary RPL had no or one pregnancy loss before the first live birth. We compared the time interval from the first to second live birth in patients with primary RPL, those with secondary RPL, and participants without RPL using generalized additive models to allow for a non-linear relationship between maternal age and time interval between first and second live births. We also compared prevalence of pregnancy complications at the first and second live births between the groups using non-parametric Kruskal-Wallis H test and Fisher's exact test for continuous and categorical variables, respectively. We assessed the cumulative second live birth rates in patients with primary RPL and those without RPL, among participants who had their first live birth between 2000 and 2010. Cox proportional hazards model was used to estimate and compare hazard ratios between the two groups using a stratified modelling approach. The adjusted time interval between the first and second live births was the longest in patients with secondary RPL, followed by individuals without RPL, and the shortest time interval was observed in patients with primary RPL: 4.34 years (95% CI: 4.09-4.58), 3.20 years (95% CI: 3.00-3.40), and 3.05 years (95% CI: 2.79-3.32). A higher frequency of pregnancy losses was associated with an increased time interval between the first and second live births. The prevalence of pregnancy complications at the first and second live births, including gestational diabetes, hypertensive disorder of pregnancy, preterm birth, and multiple gestations was significantly higher in patients with primary RPL compared with those without RPL. The cumulative second live birth rate was significantly lower in patients with primary RPL compared with individuals without RPL. This study may be limited by its retrospective nature. Although we adjusted for multiple potential confounders, there may be residual confounding due to a lack of information about pregnancy intentions and other factors, including unreported pregnancy losses. The results of this study provide information that will help clinicians in the counselling of RPL patients who desire a second child. This study was supported in part by a grant from the Canadian Institutes of Health Research (CIHR): Reference Number W11-179912. M.A.B. reports research grants from CIHR and Ferring Pharmaceutical. He is also on the advisory board for AbbVie, Pfizer, and Baxter. The other authors report no conflict of interest. NCT04360564.

A step closer to parenthood with non-obstructive azoospermia: Unveiling the impact of microdissection testicular sperm extraction in Australia's largest single-centre study.

Non-obstructive azoospermia (NOA) diagnosis poses challenges for couples seeking parenthood. Microdissection testicular sperm extraction (MD-TESE) excels in retrieving testicular sperm cells for NOA cases. However, limited live birth data in Australian NOA patients hinders accurate counselling. This study aimed to determine the likelihood of infertile couples with a male partner diagnosed with NOA conceiving biological children using MD-TESE / intracytoplasmic sperm injection (ICSI). A retrospective cohort study included 108 NOA men treated at a public fertility unit and a private fertility centre (May 2009-May 2022). live birth rate (LBR); secondary outcomes: sperm retrieval rate, pregnancy rate, and neonatal outcomes. Among 108 patients undergoing MD-TESE, the positive sperm retrieval rate (PSRR) was 64.8% (70/108). Histology best predicted sperm retrieval success, with hypo-spermatogenesis yielding a 94.1% PSRR. Age, testicular volume, and hormonal parameters had no significant impact. Mean male age: 35.4 years; mean partner age: 32.7 years. Fertilisation rate: 50.7%. LBR per initiated cycle: 58.7% (37/63); per embryo transfer: 63.8% (37/58); per initially diagnosed NOA man: 34.3% (37/108). Cumulative LBR: 74.1% (43/58); twin rate: 10.8% (4/37). No neonatal deaths or defects were observed among 47 live offspring. This study provides valuable data for counselling NOA couples on the probability of conceiving biological offspring. MD-TESE and ICSI yielded favourable PSRR (64.8%) and LBR (63.8%). However, couples should be aware that once NOA is confirmed, the chance of taking home a baby is 34%.