Association between pre-gravid body mass index and clinical outcomes in in vitro fertilization: a multicentered retrospective cohort study.

BACKGROUND: With the increasing incidence of obesity and the childbearing-age delay among women, a debate over obesity's impacts on pregnancy and neonatal outcomes becomes hot. The potential negative effects of obesity and aging on fertility lead to an idea, whether an obese female pursuing IVF treatment can benefit from an ideal BMI achieved over a long-time weight loss process at the cost of aging? We aimed to assess the association between body mass index (BMI) and clinical or neonatal outcomes in patients undergoing in vitro fertilization (IVF) treatment, for answering whether it is necessary to lose weight first for obese patients, particularly those at advanced age. METHODS: A retrospective cohort study was performed using multicentered data from China. The women were stratified into 5 groups in terms of pre-gravid BMI (kg/m2) with the WHO obesity standard (group 1: BMI < 18.5; group 2: 18.5 ≤ BMI < 23.0; group 3: 23.0 ≤ BMI < 25.0; group 4: 25.0 ≤ BMI < 30.0; group 5: BMI ≥ 30.0). The primary outcome was cumulative live birth rate (CLBR), and other clinical and neonatal outcomes were weighed as secondary outcomes. Multivariate logistic regression analyses were carried to evaluate the association between BMI and the CLBR, or between BMI and some neonatal outcomes. Furthermore, we implemented a machine-learning algorithm to predict the CLBR based on age and BMI. RESULTS: A total of 115,287 women who underwent first IVF cycles with autologous oocytes from January 2013 to December 2017 were included in our study. The difference in the CLBR among the five groups was statistically significant (P < 0.001). The multivariate logistic regression analysis showed that BMI had no significant impact on the CLBR, while women's age associated with the CLBR negatively. Further, the calculation of the CLBR in different age stratifications among the five groups revealed that the CLBR lowered with age increasing, quantitatively, it decreased by approximately 2% for each one-year increment after 35 years old, while little difference observed in the CLBR corresponding to the five groups at the same age stratification. The machine-learning algorithm derived model showed that BMI's effect on the CLBR in each age stratification was negligible, but age's impact on the CLBR was overwhelming. The multivariate logistic regression analysis showed that BMI did not affect preterm birth, low birth weight infant, small for gestational age (SGA) and large for gestational age (LGA), while BMI was an independent risk factor for fetal macrosomia, which was positively associated with BMI. CONCLUSIONS: Maternal pre-gravid BMI had no association with the CLBR and neonatal outcomes, except for fetal macrosomia. While the CLBR was lowered with age increasing. For the IVF-pursuing women with obesity plus advanced age, rather than losing weight first, the sooner the treatment starts, the better. A multicentered prospective study with a large size of samples is needed to confirm this conclusion in the future.

Number of embryos transferred could possibly be associated with angular pregnancy in in vitro fertilization-embryo transfer.

OBJECTIVE: The probability of embryo implantation in an abnormal location is significantly higher in assisted reproductive technology (ART) than in natural pregnancies. Angular pregnancy is an eccentric intrauterine pregnancy with embryo implantation in the lateral superior angle of the uterine cavity. Cycle-level factors associated with angular pregnancy in patients conceived with ART needed to be explored. METHODS: A total of 11 336 clinical pregnancies cycles were included. Angular pregnancy rate was compared among groups according to the type of embryos transferred. Among them, 53 cases of angular pregnancy and 159 cases of normal intrauterine pregnancy were screened out using propensity score matching. Risk factors of angular pregnancy were explored. RESULTS: The angular pregnancy rate was 0.31% (14/4572) in the day 5 blastocyst transfer group, 0.58% (39/6764) in non-day 5 embryo transfer group, with 0.55% (29/5280) in day 3 embryo transfer and 0.67% (10/1484) in the day 6 blastocyst group, respectively. A multifactor regression analysis was performed and indicated that the number of embryos transferred was significantly associated with angular pregnancy (P = 0.031, OR, 2.23, 95% CI: 1.09-4.68). CONCLUSION: Multiple embryo transfer could possibly be associated with an increased incidence of angular pregnancy in patients conceived with ART.

Outcomes and cost-effectiveness comparisons of progestin-primed ovarian stimulation, GnRH antagonist protocol, and luteal phase stimulation for fertility preservation.

OBJECTIVE: To compare the clinical outcomes and cost-effectiveness of progestin-primed ovarian stimulation (PPOS) and the gonadotropin-releasing hormone-antagonist (GnRH-A) protocol in fertility preservation (FP) in cancer patients. The stimulation option when patients were in the luteal phase was also explored. METHODS: This retrospective study analyzed clinical data from 163 patients who underwent FP. The number of retrieved oocytes and vitrified oocytes/embryos, total dose of gonadotropin, duration of stimulation, number of injections, and cost were compared among the PPOS, GnRH-A, and luteal phase stimulation (LPS) groups. RESULTS: No significant differences were noted in the numbers of retrieved oocytes and vitrified oocytes/embryos among the three groups. In the multiple regression model, age (P = 0.02) and antral follicle count (AFC) (P < 0.001), but not the controlled ovarian stimulation (COS) protocols (P = 0.586), were associated with the number of retrieved oocytes. The number of injections and the cost were all significantly lower in the PPOS and LPS groups than in the GnRH-A group(P < 0.001). CONCLUSION: PPOS had similar clinical results but was superior medically and economically to GnRH-A. For patients in the luteal phase, LPS was an optional protocol with similar outcomes and costs to PPOS.

Comparison of aneuploidy rate in spontaneous abortion chorionic villus between D6 and D5 thawed-frozen blastocyst transfer.

BACKGROUND: To compare the aneuploidy rate in spontaneous abortion chorionic villus (SA-CV) after D5 and D6 thawed-frozen blastocyst transfer(TBT). METHODS: This retrospective cohort study recruited 522 patients with early spontaneous abortion from March 2012 to January 2020 in the our center. The aneuploidy rate of SA-CV was compared according to the blastocyst development stage: D5 group (n = 398) and D6 group (n = 124). RESULTS: Patients' characteristics, including age, body mass index, follicle-stimulating hormone, fertilization methods, type of infertility, infertility duration, and gestational age when abortion, did not differ between the two groups (all P > 0.05). Although the mean number of embryos was significantly higher in D6 than in the D5 group (P < 0.001), the mean number of high-quality embryos was similar (P = 0.773). In the D5 group, 46.5% of SA-CV showed aneuploidy, which was comparable to 41.1% in the D6 group (P = 0.296). After further grouping according to age (> 35 years or ≤ 35 years), the difference between the D5 and D6 groups remained not statistically significant (P = 0.247 and P = 0.690). Multivariate logistic analysis showed that women's age was independently associated with the aneuploidy rate (OR = 0.891; 95% CI: [0.854-0.930]; P < 0.001). The rate of chromosomal aneuploidy was significantly higher in the age > 35 years group than in the age ≤ 35 years group (61.0% vs. 39.4%, P < 0.001). Other factors, including blastocyst formation speed, were not significant predictors of aneuploidy rate. CONCLUSIONS: The rate of chromosomal aneuploidy in SB-CV after D6 TBT was comparable to that after D5 TBT. Chromosomal aneuploidy may not be a main factor contributing to the high prevalence early pregnancy loss at D6 group.

A comparison of embryo culture strategies for women of advanced age with four or fewer available D3 embryos: a single centre retrospective analysis of 556 patients.

The purpose of this study was to compare two embryo culture strategies in older women with four or fewer D3 embryos. A total of 556 eligible patients aged >38 years in a single reproductive centre underwent IVF/ICSI leading to the generation of four or fewer D3 embryos from April 2016 to October 2018. Patients whose D3 embryos were all cultured to blastocyst were classified as group A; those in which none of their embryos was cultured to blastocysts were classified as group B. Cumulative biochemical pregnancy rate, clinical pregnancy rate and live birth rate were similar between the two groups (p = 0.582, 0.426 and 0.546, respectively). Though more embryo transfer cycles were achieved in group B, significantly higher biochemical and clinical pregnancy rate per embryo transfer cycle were found in group A (p = 0.001 and 0.003). In patients with blastocyst culture, the clinical conditions of those who had a successful outcome were better than those who failed. Blastocyst culture and transfer can significantly increase pregnancy rate per embryo transfer cycle and may be appropriate in some older patients with a good clinical prognosis.

Identification of Sialyl-Lewis(x)-Interacting Protein on Human Spermatozoa.

Capacitated spermatozoa initiate fertilization by binding to the zona pellucida (ZP). Defective spermatozoa-ZP binding causes infertility. The sialyl-Lewis(x) (SLeX) sequence is the most abundant terminal sequence on the glycans of human ZP glycoproteins involving in spermatozoa-ZP binding. This study aimed to identify and characterize the SLeX-binding proteins on human spermatozoa. By using affinity chromatography followed by mass spectrometric analysis, chromosome 1 open reading frame 56 (C1orf56) was identified to be a SLeX-binding protein of capacitated spermatozoa. The acrosomal region of spermatozoa possessed C1orf56 immunoreactive signals with intensities that increased after capacitation indicating translocation of C1orf56 to the cell surface during capacitation. Treatment with antibody against C1orf56 inhibited spermatozoa-ZP binding and ZP-induced acrosome reaction. Purified C1orf56 from capacitated spermatozoa bound to human ZP. A pilot clinical study was conducted and found no association between the percentage of capacitated spermatozoa with C1orf56 expression and in vitro fertilization (IVF) rate in assisted reproduction treatment. However, the percentage of C1orf56 positive spermatozoa in the acrosome-reacted population was significantly (P < 0.05) lower in cycles with a fertilization rate < 60% when compared to those with a higher fertilization rate, suggesting that C1orf56 may have functions after ZP-binding and acrosome reaction. A larger clinical trial is needed to determine the possible use of sperm C1orf56 content for the prediction of fertilization potential of sperm samples.

The role of galectin-3 in spermatozoa-zona pellucida binding and its association with fertilization in vitro.

Human spermatozoa can fertilize an oocyte only after post-testicular maturation and capacitation. These processes involve dynamic modification and reorganization of the sperm plasma membrane, which allow them to bind to the zona pellucida (ZP) of the oocyte. Defective sperm-ZP binding is one of the major causes of male subfertility. Galectin-3 is a secretory lectin in human seminal plasma well known for its action on cell adhesion. The aim of this study was to determine the role of galectin-3 in spermatozoa-ZP interaction and its association with fertilization rate in clinical assisted reproduction. Our studies revealed that the acrosomal region of ejaculated and capacitated spermatozoa possess strong galectin-3 immunoreactivity, which is much stronger than that of epididymal spermatozoa. Expression of galectin-3 can also be detected on seminal plasma-derived extracellular vesicles (EVs) and can be transferred to the sperm surface. Blocking of sperm surface galectin-3 function by antibody or carbohydrate substrate reduced the ZP-binding capacity of spermatozoa. Purified galectin-3 is capable of binding to ZP, indicating that galectin-3 may serve as a cross-linking bridge between ZP glycans and sperm surface glycoproteins. Galectin-3 levels in seminal plasma-derived EVs were positively associated with fertilization rates. These results suggest that galectin-3 in EVs is transferred to the sperm surface during post-testicular maturation and plays a crucial role in spermatozoa-ZP binding after capacitation. Reduced galectin-3 expression in seminal plasma-derived EVs may be a cause behind a low fertilization rate. Further studies with more clinical samples are required to confirm the relationship between galectin-3 levels and IVF outcomes.

Predictive value of initial serum human chorionic gonadotropin levels for pregnancies after single fresh and frozen blastocyst transfer.

As one of the earliest markers for predicting pregnancy outcomes, human chorionic gonadotropin (hCG) values have been inconclusive on reliability of the prediction after frozen and fresh embryo transfer (ET). In this retrospective study, patients with positive hCG (day 12 after transfer) were included to examine the hCG levels and their predictive value for pregnancy outcomes following 214 fresh and 1513 vitrified-warmed single-blastocyst transfer cycles. For patients who got clinical pregnancy, the mean initial hCG value was significantly higher after frozen cycles than fresh cycles, and the similar result was demonstrated for patients with live births (LB). The difference in hCG value existed even after adjusting for the potential covariates. The area under curves (AUC) and threshold values calculated by receiver operator characteristic curves were 0.944 and 213.05 mIU/mL for clinical pregnancy after fresh ET, 0.894 and 399.50 mIU/mL for clinical pregnancy after frozen ET, 0.812 and 222.86 mIU/mL for LB after fresh ET, and 0.808 and 410.80 mIU/mL for LB after frozen ET with acceptable sensitivity and specificity, respectively. In conclusion, single frozen blastocyst transfer leads to higher initial hCG values than single fresh blastocyst transfer, and the initial hCG level is a reliable predictive factor for predicting IVF outcomes.

Predictive Value of Initial Serum Human Chorionic Gonadotropin Levels for Pregnancies after Single Fresh and Frozen Blastocyst Transfer / 华中科技大学学报（医学）（英德文版）

As one of the earliest markers for predicting pregnancy outcomes,human chorionic gonadotropin (hCG) values have been inconclusive on reliability of the prediction after frozen and fresh embryo transfer (ET).In this retrospective study,patients with positive hCG (day 12 after transfer) were included to examine the hCG levels and their predictive value for pregnancy outcomes following 214 fresh and 1513 vitrified-warmed single-blastocyst transfer cycles.For patients who got clinical pregnancy,the mean initial hCG value was significantly higher after frozen cycles than fresh cycles,and the similar result was demonstrated for patients with live births (LB).The difference in hCG value existed even after adjusting for the potential covariates.The area under curves (AUC) and threshold values calculated by receiver operator characteristic curves were 0.944 and 213.05 mIU/mL for clinical pregnancy after fresh ET,0.894 and 399.50 mIU/mL for clinical pregnancy after frozen ET,0.812 and 222.86 mIU/mL for LB after fresh ET,and 0.808 and 410.80 mIU/mL for LB after frozen ET with acceptable sensitivity and specificity,respectively.In conclusion,single frozen blastocyst transfer leads to higher initial hCG values than single fresh blastocyst transfer,and the initial hCG level is a reliable predictive factor for predicting IVF outcomes.

Cell membrane proteins from oviductal epithelial cell line protect human spermatozoa from oxidative damage.

OBJECTIVE: To study the potential protective action in vitro of oviductal epithelial cell membrane proteins against oxidative damage in human spermatozoa. DESIGN: Prospective in vitro study. SETTING: University research laboratory and infertility clinic. PATIENT(S): Semen from men attending the infertility clinic at the Queen Mary Hospital with normal semen parameters (World Health Organization, 2010). INTERVENTION(S): We studied the effect of oviductal epithelial cell membrane proteins on the sperm functions and endogenous antioxidant enzyme activities. MAIN OUTCOME MEASURE(S): Sperm motility, lipid peroxidation, DNA fragmentation, intracellular reactive oxygen species (ROS) level, superoxide dismutase, and glutathione peroxidase activities. RESULT(S): Oviductal epithelial cell membrane proteins bind to the human spermatozoa and protect them from ROS-induced damages in terms of sperm motility, membrane integrity, DNA integrity, and intracellular ROS level. Spermatozoa-oviduct epithelial cell interaction also enhances the antioxidant defenses in spermatozoa. CONCLUSION(S): Our results demonstrated the protective effects of spermatozoon-oviductal epithelial cell interaction against oxidative stress in human spermatozoa. The results enhance our understanding of the protective mechanism of oviduct on sperm functions.