Effect of diminished ovarian reserve on the outcome of fresh embryo transfer in IVF/ICSI cycles among young women: A retrospective cohort study.

OBJECTIVE: This study aims to investigate the effect of diminished ovarian reserve (DOR) on the clinical outcomes and maternal and infant safety of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) procedures in young women aged ≤ 35 years. METHODS: A retrospective cohort study was performed to analyze the clinical data of 4,203 infertile women aged ≤ 35 years who underwent fresh embryo transfer (ET) in IVF/ICSI cycles. The data were collected from their initial visits to Fujian Maternity and Child Health Hospital between January 2015 and January 2022. Based on their ovarian reserve, the participants were categorized into two groups: DOR group (n = 1,027) and non-DOR group (n = 3,176). A propensity score matching (PSM) method was employed to ensure a relatively balanced distribution of covariates. The primary outcome assessed in this study was the live birth rate, while the secondary observation indicators included rates of high-quality embryo development, blastocyst formation, clinical pregnancy, and miscarriage, along with perinatal complications, neonatal birth weight, and the incidence of low birth weight (LBW). RESULTS: The DOR group showed notably lowered rates of blastocyst formation (59.8% vs. 64.1%), embryo implantation (29.8% vs.33.3%), clinical pregnancy (47.9% vs. 53.6%), and live birth (40.6% vs. 45.7%) compared to the non-DOR group (all P < 0.05). However, no statistically significant differences were observed in the high-quality embryo rate, miscarriage rate, perinatal complications, neonatal birth weight, or LBW incidence in infants between both groups (all P > 0.05). CONCLUSION: DOR has been found to reduce both clinical pregnancy and live birth rates in young females undergoing fresh ET in IVF/ICSI cycles. However, this reduction does not increase the risk of perinatal complications or LBW of infants through live birth cycles.

Effect of male HBV infection on the outcomes of IVF/ICSI cycles: a retrospective cohort study based on propensity score matching.

ABSTRACT: This study aimed to investigate the effects of male hepatitis B virus (HBV) infection on male fertility, embryonic development, and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes. We performed a retrospective cohort study that included 3965 infertile couples who received fresh embryo transfer cycles for the first time at the Fujian Maternity and Child Health Hospital (Fuzhou, China) from January 2018 to January 2021. Infertile couples were categorized based on their HBV infection status into the HBV group (HBV-positive men and HBV-negative women) and the control group (HBV-negative couples). A 1:1 propensity score matching was performed with relatively balanced covariates. Baseline characteristics, semen parameters, laboratory outcomes, clinical outcomes, and obstetric and neonatal outcomes were compared between groups. After propensity score matching, 821 couples were included in each group. Both groups had similar semen parameters and obstetric and neonatal outcomes. The HBV group showed a significantly lower live birth rate than the control group (P < 0.05). The HBV group had a significantly higher abortion rate than the control group (P < 0.05). The rates of high-quality embryos and blastocyst formation were significantly lower in the HBV group than those in the control group (both P < 0.05). In conclusion, in couples who undergo IVF/ICSI, male HBV infection reduces the live birth rate and increases the risk of miscarriage. However, the incidence of low birth weight in women with IVF/ICSI does not increase with male HBV infection.

Mfn2 regulates mitochondria-associated ER membranes to affect PCOS oocyte development.

This study aimed to investigate the role of mitochondrial-related protein Mfn2 in polycystic ovary syndrome (PCOS) and its impact on oocyte development. The pathological features of PCOS model mice were confirmed by hematoxylin-eosin staining and immunohistochemistry. The expression of Mfn2 and mitochondrial-related proteins in PCOS oocytes and granulosa cells was detected by qRT-PCR and Western blot. Mitochondrial quantity was measured by Mito-Tracker staining, and the structure of mitochondria-associated ER membranes (MAMs) was observed by transmission electron microscopy. The results showed that Mfn2 was significantly downregulated in PCOS oocytes and granulosa cells, and its expression was inhibited in oocytes at different developmental stages. Moreover, the structure of MAMs was also disrupted. Downregulation of Mfn2 expression led to a reduction in mitochondrial quantity in oocytes and granulosa cells, as well as disruption of MAM structure, while overexpression of Mfn2 had the opposite effect. In conclusion, this study indicates that Mfn2 affects the development of PCOS oocytes by regulating MAMs and may be involved in maintaining the stability of MAM structure and function, thereby affecting mitochondrial quantity and function. These findings provide new insights into the pathogenesis and treatment of PCOS.

Development and validation of a nomogram model for predicting clinical pregnancy in endometriosis patients undergoing fresh embryo transfer.

PURPOSE: To construct and validate a nomogram model for predicting clinical pregnancy in individuals with endometriosis undergoing fersh embryo transfer (ET). METHODS: A retrospective analysis was conducted on 1630 individuals with endometriosis who underwent in vitro fertilization (IVF) with fresh embryo transfer at the Reproductive Medicine Center of Fujian Maternity and Child Health Hospital from January 2018 to January 2022. The research population was sorted into two groups through random sampling, namely, the model group (n = 1141) and the validation group (n = 489), with a ratio of 7:3. Univariate analysis was utilized to determine the influencing factors for clinical pregnancy in the model group. The LASSO algorithm was utilized to select the optimal matching factors, which were then included in a multifactorial forward stepwise logistic regression to determine independent influencing factors and develop a nomogram. The discrimination, accuracy, and clinical efficacy of the prediction model were analyzed utilizing the receiver operating characteristic (ROC) curve, calibration curve, and clinical decision curve. RESULTS: Through multivariate-logistic-regression analysis, these factors were identified as independent influencing factors for the clinical pregnancy in endometriosis patients undergoing fresh embryo transfer: female age (OR = 0.933, 95% CI = 0.902-0.965, P < 0.001), ASRM stage (OR = 0.384, 95% CI = 0.276-0.532, P < 0.001), postoperative to IVF duration (OR = 0.496, 95% CI = 0.356-0.688, P < 0.001), antral follicle count (AFC) (OR = 1.076, 95% CI = 1.013-1.161, P = 0.045), anti-Müllerian hormone (AMH) (OR = 1.202, 95% CI = 1.073-1.35, P = 0.002), Gonadotrophin-releasing hormone (GnRH) agonist protocol (OR = 1.536, 95% CI = 1.109-2.131, P = 0.01), number of oocytes retrieved (OR = 1.154, 95% CI = 1.067-1.249, P < 0.001), number of high-quality cleavage embryos (OR = 1.261, 95% CI = 1.164-1.369, P < 0.001), and number of embryos transferred (OR = 1.957, 95% CI = 1.435-2.679, P < 0.001). A prediction model for estimating the clinical pregnancy probability in individuals with endometriosis was constructed per these identified independent factors. The ROC showed an area under the curve (AUC) of 0.807 (95% CI = 0.782-0.832) in the model group and 0.800 (95% CI = 0.761-0.84) in the validation group. The Hosmer-Lemeshow test demonstrated no statistically significant difference between predicted and actual clinical pregnancy probabilities (P > 0.05). The clinical decision curve demonstrated that both the model and the validation groups achieved maximum net benefit at threshold probability values of 0.08-0.96 and 0.16-0.96, indicating good clinical efficacy within this range of threshold probabilities. CONCLUSION: Female age, ASRM stage, postoperative to IVF duration, stimulation protocol, AFC, AMH, number of oocytes retrieved, number of high-quality cleavage embryos and number of transferred embryos are independent influencing factors for the clinical pregnancy rate in individuals with endometriosis receiving fresh embryo transfer. The nomogram model based on these factors demonstrates good clinical predictive value and efficacy, providing a basis for clinical prognosis, intervention, and individualized medical treatment planning.

Analysis of relative factors and prediction model for optimal ovarian response with gonadotropin-releasing hormone antagonist protocol.

Objective: To explore the relative factors for best ovarian response in patients undergoing assisted reproductive technology with the gonadotropin-releasing hormone antagonist protocol and to establish a nomogram prediction model of ovarian response. Methods: A retrospective cohort analysis of the clinical data of 1,944 patients who received assisted reproductive treatment in the Center for Reproductive Medicine of Fujian Maternity and Child Health Hospital from April 1, 2018, to June 30, 2020. According to the number of oocytes obtained, there were 659 cases in the low ovarian response group (no more than five oocytes were retrieved), 920 cases in the normal ovarian response group (the number of retrieved oocytes was >5 but ≤18), and 365 cases in the high ovarian response group (>18 oocytes retrieved). Independent factors affecting ovarian responsiveness were screened by logistic regression, which were the model entry variables, and a nomogram prediction model was established based on the regression coefficients. Results: There were statistically significant differences in age, anti-Mullerian hormone, antral follicle count, the diagnosis of endometriosis, decreased ovarian reserve, polycystic ovary syndrome, basal follicle-stimulating hormone and basal luteinizing hormone among the three groups (P < 0.001). Multifactorial stepwise regression analysis showed that female age (0.95 [0.92-0.97], P = 0.000), decreased ovarian reserve (0.27 [0.19-0.38]), P = 0.000), endometriosis (0.81 [0.56-0.86], P = 0.000), antral follicle count (1.09 [1.06-1.12], P = 0.000), basal follicle-stimulating hormone (0.90 [0.85-0.96], P = 0.001), Anti-Mullerian hormone (1.19 [1.13-1.26], P= 0.000) and luteinizing hormone on trigger day (0.73 [0.66-0.80], P= 0.000), were independent factors for the occurrence of different ovarian responses during ovarian hyperstimulation. The predictive model of ovarian responsiveness was constructed based on the above factors, and the model was verified with 589 patients' data from July 1, 2020, to December 31, 2020, at this center. The predicted ovarian response (number of eggs obtained) of a total of 450 patients was consistent with the actual results, with a coincidence degree of 76.4%, and the consistency index of the model is 0.77. Conclusion: The nomogram model was successfully developed to effectively, intuitively, and visually predict the ovary reactivity in the gonadotropin-releasing hormone antagonist protocol and provide guidance for clinical practice.

Effect of cumulin and super-GDF9 in standard and biphasic mouse IVM.

PURPOSE: In vitro maturation (IVM) is a technology that generates mature oocytes following culture of immature cumulus-oocyte complexes (COC) in vitro. IVM is characterized by minimal patient stimulation, making it attractive for certain patient groups. Recently, a biphasic IVM system, capacitation (CAPA)-IVM, has shown improved clinical outcomes relative to standard IVM; however, it remains less efficient than IVF. This study assessed whether supplementation of CAPA-IVM culture media with the novel TGFß superfamily proteins cumulin and super-GDF9 improves subsequent mouse embryo development. METHODS: Immature mouse COCs were cultured by standard IVM or biphasic IVM ± cumulin or super-GDF9. RESULTS: Both cumulin and super-GDF9 in standard IVM significantly improved day-6 blastocyst rate (53.9% control, 73.6% cumulin, 70.4% super-GDF9; p = 0.006; n = 382-406 oocytes). Cumulin or super-GDF9 in CAPA-IVM did not alter embryo yield or blastocyst cell allocation in an unstimulated model. Moreover, cumulin did not alter these outcomes in a mild PMSG stimulation model. Cumulin in CAPA-IVM significantly increased cumulus cell expression of cumulus expansion genes (Ptgs2, Ptx3, Adamts1, Gfat2) and decreased Lhr expression relative to control. However, cumulin-induced mRNA expression of cumulus cell (Ptgs2, Ptx3) and oocyte genes (Gdf9, Bmp15, Oct4, Stella) in CAPA-IVM remained significantly lower than that of in vivo matured cells. CONCLUSION: Cumulin did not provide an additional beneficial effect in biphasic IVM in terms of blastocyst yield and cell allocation; however in standard IVM, cumulin and super-GDF9 significantly improve oocyte developmental competence.

Comparison between oral and vaginal estrogen usage in inadequate endometrial patients for frozen-thawed blastocysts transfer.

UNLABELLED: Endometrial preparation with exogenous estrogen is a common practice in frozen-thawed embryo transfer (FET) cycles. The objective of this study was to compare the clinical outcomes of two endometrial preparation groups, oral estradiol valerate tablets (OEV) group versus vaginal estradiol (VE) tablets group, in inadequate endometrium patients. This retrospective, single-center, cohort study of patients undergoing FET treatment between Jan. 2012 and Jun. 2013, at an academic IVF center, included 247 patients (cycles) with endometrial thickness < 8 mm on day 13 of the hormone replacement cycle: OEV group included 69 patients (cycles) who received continuous OEV from day 1 onwards up to the day of progesterone supplement, while VE group included 178 patients (cycles) who taken OEV from day 1 to day 12, and used VE tablets from day 13 till the day of progesterone supplement. Patients in VE group required more days and higher dosage of estradiol, but had thinner endometrium on the day of transfer. However, the increase of endometrial thickness was more, when compared to OEV-treated patients. The implantation rate and pregnancy rate were, though not significantly, higher in VE group. CONCLUSIONS: Longer time of administration and higher dosage of estradiol usage did not have adverse effects on the clinical pregnancy rate. VE tablets may promote endometrial development and pregnancy success in FET cycles could not verify. Further study is needed to confirm the vaginal estradiol action on frozen-thawed embryo transfer cycles.

Surgical treatment for endometrioma does not increase clinical pregnancy rate or live birth/ongoing pregnancy rate after fresh IVF/ICSI treatment.

The impact of surgical treatment for endometrioma prior to assisted reproductive treatment (ART) on pregnancy outcomes remains controversy. The aim of this study is to investigate whether surgery provides benefits in subsequent ART outcomes. We retrospectively analyzed the data of 292 patients who underwent their first attempted IVF/ICSI treatment at fertility center in a university hospital, from 2011 to 2013. The primary outcomes included clinical pregnancy rate (CPR), live birth/ongoing pregnancy rate (LB/OPR). Although patients with no history of surgery and with visual endometriomas during IVF/ICSI treatment had fewer antral follicles (9.3±4.9 vs. 11.0±5.3, P=0.046), and required higher dosage of gonadotropin (3122.8±1118.1 vs. 2741.7±1096.0, P=0.043) when compared to patients who underwent surgery for endometriomas and without visual endometriomas during IVF/ICSI, the CPR and LB/OPR was not significantly affected (OR=0.771, 95%CI=0.398-1.495, and OR=1.043, 95%CI=0.526-2.069, respectively). In conclusion, surgical treatment does not significantly improve pregnancy outcomes in patients who plan to take IVF/ICSI treatment.

Effect of overweight/obesity on IVF-ET outcomes in chinese patients with polycystic ovary syndrome.

The purpose of this study was to investigate the impact of body mass index (BMI) on the outcomes of IVF/ICSI treatment cycles in Chinese patients with polycystic ovary syndrome (PCOS). Women with PCOS (n = 128) and tubal factor (n = 128) underwent a conventional long GnRH agonist suppressive protocol. Women with PCOS had significantly more oocytes retrieved (P < 0.05) and available embryos (P < 0.05), as compared to patients with tubal infertility. No significant differences were observed in clinical pregnancy rate, miscarriage rate and live birth rate between two groups. Patients were further divided into two subgroups. In total, 49 patients in PCOS group and 19 patients in tubal factor group were overweight or obese (BMI ≥ 24 kg/m(2)). Lean women (BMI < 24 kg/m(2)) with PCOS showed higher clinical pregnancy rate (P < 0.05). Live birth rate and miscarriage rate were also higher in lean PCOS women, but the differences were not significant. Similar clinical outcomes of IVF/ICSI success were achieved between two subgroups in tubal factor patients. In conclusion, lean PCOS patients obtained higher clinical pregnancy rate compared with overweight/obese PCOS patients in Chinese populations.

The impact of endometriosis on IVF/ICSI outcomes.

This retrospective cohort study was aimed to investigate the impact of endometriosis on the IVF/ICSI outcomes. A total of 1027 cycles of patients undergoing IVF/ICSI treatment in a reproductive medicine unit of academic hospital were enrolled. In the present study, 431 cycles of patients with endometriosis constituted the study group, including 152 cycles of patients with stage I-II endometriosis and 279 cycles of patients with stage III-IV endometriosis, while 596 cycles of patients with tubal factors infertility were considered as the control group. Ovarian stimulation parameters and IVF/ICSI outcomes were compared. Patients with stage I-II and stage III-IV endometriosis required higher dosage and longer duration of gonadotropins, but had lower day 3 high-quality embryos rate, when compared to patients with tubal infertility. In addition, the number of oocytes retrieved, the number of obtained embryos, the number of day 3 high-quality embryos, serum E2 level on the day of hCG, fertilization rate were lower in patients with stage III-IV endometriosis than those in tubal factors group. Except reduced implantation rate in stage III-IV endometriosis group, no differences were found in other pregnancy parameters. This study suggests that IVF/ICSI yielded similar pregnancy outcomes in patients with different stages of endometriosis and patients with tubal infertility. Therefore, IVF/ICSI can be considered as an effective approach for managing endometriosis-associated infertility.

Does progesterone-induced endometrial withdrawal bleed before ovulation induction have negative effects on IUI outcomes in patients with polycystic ovary syndrome?

Polycystic ovary syndrome is a common heterogeneous endocrine disorder in reproductive-age women, with prevalence around 4-12%. The present study was performed to investigate whether progesterone-induced endometrial bleed before ovulation induction affects pregnancy in patients with PCOS who underwent intrauterine insemination (IUI) treatment. A total of 241 IUI cycles were retrospectively analyzed. Patients enrolled in this study underwent ovulation induction with IUI treatment from Jan. 2011 to Dec. 2012. The study group consisted of 184 cycles with progesterone-withdrawal bleed before ovulation induction. The control group included 57 cycles with spontaneous menses. The clinical characteristics, ovulation induction parameters and IUI outcomes, such as pregnancy rate and live birth/ongoing pregnancy rate, were compared between the two groups. We found that patients in induced shedding group had thinner peak endometrium in ovulation induction cycles. Additionally, the ratio of peak endometrial-thickness to baseline endometrial-thickness was lower in induced menses patients. However, the pregnancy rate and live birth/ongoing pregnancy rate per cycle were similar with the control group. Excluding the peak E(2) level, peak E(2)/number of follicles > 15 mm and peak endometrial-thickness/baseline endometrial-thickness, no differences were found in ovulation induction or IUI results between patients used Letrozole or Clomiphene Citrate. In patients undergoing administration with Letrozole, those taking progesterone had thinner endometrium and lower peak endometrial-thickness/baseline endometrial-thickness. However, the pregnancy rate and live birth/ongoing pregnancy rate were not statistically different from patients with spontaneous menses. In conclusion, our study showed that progesterone exerted a negative effect on endometrial development, which seemed to be associated with reduced pregnancy results in ovulation induction with IUI cycles.