Bisphenol a downregulates GLUT4 expression by activating aryl hydrocarbon receptor to exacerbate polycystic ovary syndrome.

BACKGROUND: Bisphenol A (BPA) levels are high in women with polycystic ovary syndrome (PCOS). The mechanism by which BPA induces abnormal glucose metabolism in PCOS patients is largely unknown. METHODS: Serum and urine samples were collected from women with and without PCOS (control) at the reproductive medicine center with informed consent. Non-PCOS patients who received in vitro fertilization were recruited for collection of ovarian follicular fluid and granular cells. Wild-type C57BL/6 and AhR -/- mice were used to verify the effects of BPA on PCOS. Real-time PCR, western blotting, and ELISA were conducted to analyze the function of BPA. Chip-qPCR verified the role of AhR in GLUT4 transcription. Flow cytometry was performed to determine glucose uptake. RESULTS: A positive correlation was observed between BPA concentration and serum BPA levels in PCOS patients. BPA aggravated the changes in PCOS with abnormal glucose metabolism, impaired fertility, and increased body fat. Mechanistically, we showed that BPA activated AhR and led to decreased glucose transport via GLUT4 downregulation in ovarian granular cells. Therefore, the use of inhibitors or knockout of AhR could effectively rescue BPA-induced metabolic disorders in PCOS mice. CONCLUSIONS: Our results revealed that BPA suppressed GLUT4 expression and induced abnormal glucose metabolism by activating AhR, causing insulin resistance, and is thus a potential contributor to the development of PCOS. Therefore, AhR could be a potential new therapeutic target for PCOS. Video Abstract.

Impact of mildly evaluated thyroid-stimulating hormone levels on in vitro fertilization or intracytoplasmic sperm injection outcomes in women with the first fresh embryo transfer: a large study from China.

PURPOSE: This study aimed to investigate the association between mild elevation of thyroid-stimulating hormone (TSH) levels and pregnancy outcomes of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatments in women with the first fresh embryo transfer. METHODS: Large single-center retrospective cohort study of 15,728 patients from January 2018 to December 2022 were enrolled in the analyses. Clinical pregnancy rates, live birth rates, miscarriage rates, and ectopic pregnancy rates were compared between the TSH levels < 2.5 mIU/L group (N = 10,932) and TSH levels ≥ 2.5 mIU/L group (N = 4796). Subgroup analysis was performed for patients with TSH levels ≥ 2.5 mIU/L, dividing them into the thyroid peroxidase antibody (TPO)-negative group (N = 4524) and the TPO-positive group (N = 272). RESULTS: There were no significant differences in the aforementioned pregnancy outcomes between the TSH levels < 2.5 mIU/L group and TSH levels ≥ 2.5 mIU/L group. Similarly, no significant differences were observed in the pregnancy outcomes between the TPO-negative group and the TPO-positive group. CONCLUSION: Mildly elevated pre-conception TSH levels in thyroid-normal infertile patients did not have an impact on pregnancy outcomes of IVF/ICSI treatments.

High anti-Müllerian hormone (AMH) is associated with increased risks of ectopic pregnancy in women undergoing fresh embryo transfer cycle, a cohort study.

BACKGROUND: Ectopic pregnancy is more common amongst assisted reproduction cycles and is a cause of significant maternal morbidity. Few predictive markers exist to help identify and modify risk of ectopic pregnancy in preparing for embryo transfer. The relationship between serum and AMH and ectopic pregnancy rate is unknown. METHODS: This was a retrospective cohort study investigating women who underwent fresh embryo transfer cycles from January 2017 to December 2019 in Peking University Third Hospital. The primary outcome was ectopic pregnancy. Restricted cubic splines with four knots for AMH concentration (0-3, 3-6, 6-12, 12-max) were used to map out the non-linear relationship between the predicted ectopic pregnancy rate and the serum AMH concentration. Log binomial regression was used to test the crude risk ratio (cRR) and the adjusted risk ratio (aRR) after adjustment for confounders with 95% confidence intervals (CI) to determine the difference across various groups. RESULTS: A total of 13,718 cycles in women undergoing fresh embryo transfer were eligible for analysis. The ectopic pregnancy rate was 1.3% per embryo transfer cycle initiated and 3.3% per pregnancy. Serum AMH concentrations were higher amongst women with ectopic pregnancy than in women with a confirmed intrauterine pregnancy or heterotopic pregnancy or who did not become pregnant (Mean levels: 4.0 ng/ml vs 3.2 ng/ml, 1.7 ng/ml, and 2.8 ng/ml). An AMH concentration of 7 ng/ml represented the best cut-off value to predict ectopic pregnancy. The ectopic pregnancy rate was 3.4% per cycle and 7.5% per pregnancy in women with AMH levels ≥ 7 ng/ml; and 1.2% per cycle and 2.9% per pregnancy in women with AMH levels < 7 ng/ml. Serum AMH concentration ≥ 7 ng/ml was associated with an increased risk of ectopic pregnancy in all fresh embryo transfer cycles started (aRR = 2.35 (1.45, 3.58)) as well in women who became pregnant (aRR = 2.23 (1.49, 3.33). CONCLUSIONS: Baseline AMH concentration ≥ 7 ng/ml is associated with an increased risk of ectopic pregnancy in fresh embryo transfer cycles.

Advances in clinical applications of kisspeptin-GnRH pathway in female reproduction.

BACKGROUND: Kisspeptin is the leading upstream regulator of pulsatile and surge Gonadotrophin-Releasing Hormone secretion (GnRH) in the hypothalamus, which acts as the key governor of the hypothalamic-pituitary-ovary axis. MAIN TEXT: Exogenous kisspeptin or its receptor agonist can stimulate GnRH release and subsequent physiological gonadotropin secretion in humans. Based on the role of kisspeptin in the hypothalamus, a broad application of kisspeptin and its receptor agonist has been recently uncovered in humans, including central control of ovulation, oocyte maturation (particularly in women at a high risk of ovarian hyperstimulation syndrome), test for GnRH neuronal function, and gatekeepers of puberty onset. In addition, the kisspeptin analogs, such as TAK-448, showed promising agonistic activity in healthy women as well as in women with hypothalamic amenorrhoea or polycystic ovary syndrome. CONCLUSION: More clinical trials should focus on the therapeutic effect of kisspeptin, its receptor agonist and antagonist in women with reproductive disorders, such as hypothalamic amenorrhoea, polycystic ovary syndrome, and endometriosis.

Risk factors for twin pregnancy in women undergoing double cleavage embryo transfer.

BACKGROUND: Two or more embryo transfers have been used to increase the success rate of live birth in traditional in vitro fertilization (IVF) strategy at the expense of increased risks of multiple pregnancy and adverse perinatal outcomes. The decision regarding the elective single embryo transfer or double embryo transfer remains inconclusive. The aim of this study was to investigate the risk factors for twin pregnancy in IVF. METHODS: Participants who underwent their first fresh IVF cycle where two cleavage stage embryos were transferred in Women's Hospital of Zhejiang University between January 2010 and December 2018 were included in this retrospective cohort study. The primary outcome was twin delivery. Secondary outcomes included preterm birth and low birth weight RESULTS: Fifteen thousand four hundred fifty-nine women were available for final analysis, in which 1511 women resulted in twin delivery and 4788 women had singleton delivery. Female age over 35 was associated with reduced rates of twin pregnancy compared with female age at or less than 35 (9.5% vs 25.1%, aRR = 0.38 (0.27. 0.55)). Poor-type endometrium was associated with reduced rates of twin pregnancy (19.2% vs 27.5%, aRR = 0.75 (0.58. 0.96)). Two good-quality embryos for transfer was associated with significantly higher rates of twin pregnancy compared with one good-quality or none good-quality embryo (26% vs 12.8% vs 9.3%, aRR = 0.56 (0.45. 0.70), aRR = 0.44(0.26. 0.74)). Female age over 35 and none or one good-quality embryo for transfer were associated with reduced rate of low birth weight and preterm birth. CONCLUSION: Women with age over 35, poor-type endometrium, one good-quality embryo or none good-quality embryo were associated with reduced rate for twin pregnancy.

Arsenic exposure during juvenile and puberty significantly affected reproductive system development of female SD rats.

Infertility affects about 10-15% couples over the world, among which a large number of cases the underlying causes are still unclear. Recent studies suggest that environmental factors may play an important role in these idiopathic infertilities. Arsenic is a heavy metal found in drinking water over the world. Its effect on the development of female reproductive system at the environmental-relevant levels is still largely unknown. To test the hypothesis that arsenic exposure during juvenile and puberty may affect sex maturation and female reproductive system development, SD rats of 3 weeks of age were exposed to arsenic with environmental-relevant levels (0, 0.02, 0.2, or 2 mg/L, n = 16/group) through drinking water for about 44 days until the rats reached adulthood (65 days of age). Arsenic exposure significantly reduced the weights of both ovary and uterus without affecting the body weight. Also, arsenic exposure disturbed estrus cycles and reduced the numbers of primordial follicles and corpora lutea while increased atretic follicles. In addition, arsenic reduced serum levels of estradiol, progesterone and testosterone but increased LH and FSH levels in dose-dependent manners. QPCR and Western blot experiments indicated arsenic selectively down-regulated ovarian steroidogenic-related proteins FSHR, STAR, CYP17A1, HSD3B1 and CYP19A1 and signaling molecules PKA-ERK-JNK-cJUN, without affecting AKT and CREB. As about reproductive capacity, arsenic-exposed dams had smaller pups, reduced litter size and lower number of male pups without a change in female pups. In conclusion, juvenile and pubertal arsenic exposures at environmental-relevant levels significantly reduced reproductive functions and capacity by adult. Since the lowest effective dose is very close to the government safety standards, the relevancy of arsenic over exposure to reproductive defects in human deserves further study.

Anti-Müllerian hormone in guiding the selection of a freeze-all versus a fresh embryo transfer strategy: a cohort study.

PURPOSE: To explore an interaction effect between serum anti-Müllerian hormone (AMH) levels and the relative treatment effect of a freeze-all versus a fresh embryo transfer strategy on live birth. METHODS: This was a retrospective cohort study investigating couples with infertility and eligible for both freeze-all and fresh embryo transfer between 2017 and 2019. Women with an absolute indication for a freeze-all strategy were excluded. Multivariable fractional polynomial interaction analysis within a logistic regression model was used to evaluate whether the treatment effect of a freeze-all versus a fresh transfer strategy varied at different AMH levels. Non-linear interactions were also considered. The primary outcome was the live birth after the first transfer. RESULTS: A total of 13,503 women underwent a fresh embryo transfer and 2247 women underwent a freeze-all strategy. Live birth rates were slightly higher in the freeze-all group compared to those in the fresh embryo transfer group (35% vs 33%). There was a non-linear interaction between baseline serum AMH levels and the relative treatment effect of a freeze-all strategy versus a fresh transfer strategy on live birth (P = 0.0161). The benefit on live birth from a freeze-all embryo transfer strategy was greatest in women with a high serum level (> 7 ng/ml). The interaction remained valid when different imputation methods were used. CONCLUSION: As serum AMH level increased, there was a nonlinear increase in relative treatment effect of a freeze-only transfer versus a fresh transfer strategy on live birth, and such an effect reaches its maximum in women with high AMH levels.

GnRH agonist and hCG (dual trigger) versus hCG trigger for follicular maturation: a systematic review and meta-analysis of randomized trials.

BACKGROUND: Traditionally, final follicular maturation is triggered by a single bolus of human chorionic gonadotropin (hCG). This acts as a surrogate to the naturally occurring luteinizing hormone (LH) surge to induce luteinization of the granulosa cells, resumption of meiosis and final oocyte maturation. More recently, a bolus of gonadotropin-releasing hormone (GnRH) agonist in combination with hCG (dual trigger) has been suggested as an alternative regimen to achieve final follicular maturation. METHODS: This study was a systematic review and meta-analysis of randomized trials evaluating the effect of dual trigger versus hCG trigger for follicular maturation on pregnancy outcomes in women undergoing in vitro fertilization (IVF). The primary outcome was the live birth rate (LBR) per started cycle. RESULTS: A total of 1048 participants were included in the analysis, with 519 in the dual trigger group and 529 in the hCG trigger group. Dual trigger treatment was associated with a significantly higher LBR per started cycle compared with the hCG trigger treatment (risk ratio (RR) = 1.37 [1.07, 1.76], I2 = 0%, moderate evidence). There was a trend towards an increase in both ongoing pregnancy rate (RR = 1.34 [0.96, 1.89], I2 = 0%, low evidence) and implantation rate (RR = 1.31 [0.90, 1.91], I2 = 76%, low evidence) with dual trigger treatment compared with hCG trigger treatment. Dual trigger treatment was associated with a significant increase in clinical pregnancy rate (RR = 1.29 [1.10, 1.52], I2 = 13%, low evidence), number of oocytes collected (mean difference (MD) = 1.52 [0.59, 2.46), I2 = 53%, low evidence), number of mature oocytes collected (MD = 1.01 [0.43, 1.58], I2 = 18%, low evidence), number of fertilized oocytes (MD = 0.73 [0.16, 1.30], I2 = 7%, low evidence) and significantly more usable embryos (MD = 0.90 [0.42, 1.38], I2 = 0%, low evidence). CONCLUSION: Dual trigger treatment with GnRH agonist and HCG is associated with an increased live birth rate compared with conventional hCG trigger. TRIAL REGISTRATION: CRD42020204452 .

Endometrial thickness in the prediction of neonatal adverse outcomes in frozen cycles for singleton pregnancies.

RESEARCH QUESTION: Does endometrial thickness (EMT) predict adverse neonatal outcomes in singleton pregnancies after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) frozen embryo transfer (FET)? DESIGN: This retrospective study involved 13,383 women undergoing IVF/ICSI FET cycles between January 2010 and December 2018 in Women's Hospital of Zhejiang University. The primary outcome was preterm delivery (PTD). The secondary outcomes were small for gestational age (SGA), large for gestational age (LGA) and low birthweight (LBW). RESULTS: A total of 13,383 FET cycles resulting in 5220 singleton live births and 8163 failed cycles were included. Multiple spline regression visualization showed an increasing risk of PTD and LBW for a thin EMT. By comparing multiple cut-off points using area under the curve, a cut-off point of 8 mm was identified, which was used to categorize EMT. A reference point of EMT greater than 8 mm was used; after adjusting for covariates, individuals with EMT less than 8 mm had an adjusted odds ratio of 1.75 (95% CI 1.30 to 2.34) for PTD, 1.57 (95% CI 1.09 to 2.26) for LBW, 0.97 (95% CI 0.63 to 1.50) for SGA and 1.04 (95% CI 0.79 to 1.37) for LGA. Additional analyses showed similar increasing risk with a thin endometrium for both PTD with and without caesarean section, and PTD with low and normal birthweight percentiles. CONCLUSION: A clinical cut-off point of 8 mm has been identified, below which risk of PTD and LBW increases in women undergoing IVF/ICSI.

Association of parental prepregnancy BMI with neonatal outcomes and birth defect in fresh embryo transfer cycles: a retrospective cohort study.

BACKGROUND: Parental body mass index (BMI) is associated with pregnancy outcomes. But the effect of parental prepregnancy BMI on offspring conceived via in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), especially the birth defect, remains to be determined. This study aimed to investigate the associations of parental prepregnancy BMI with neonatal outcomes and birth defect in fresh embryo transfer cycles. METHODS: We conducted a retrospective cohort study including 5741 couples in their first fresh IVF/ICSI cycles admitted to Women's Hospital, School of Medicine, Zhejiang University from January 2013 to July 2016. The primary outcome was birth defects, which was classified according to the International Classification of Diseases, 10th Revision. Secondary outcomes included preterm delivery rate, infant gender, birth weight, small-for-gestational age (SGA) and large-for-gestational age (LGA). Multilevel regression analyses were used to assess the associations of parental prepregnancy BMI with neonatal outcomes and birth defect. RESULTS: In singletons, couples with prepregnancy BMI ≥25 kg/m2 had higher odds of LGA than those with BMI < 25 kg/m2. The birth defect rate was significantly higher when paternal prepregnancy BMI ≥25 kg/m2 in IVF cycles (aOR 1.82, 95% CI 1.06-3.10) and maternal BMI ≥25 kg/m2 in ICSI cycles (aOR 4.89, 95% CI 1.45-16.53). For subcategories of birth defects, only the odds of congenital malformations of musculoskeletal system was significantly increased in IVF offspring with paternal BMI ≥25 kg/m2 (aOR 4.55, 95% CI 1.32-15.71). For twins, there was no significant difference among four groups, except for the lower birth weight of IVF female infants. CONCLUSIONS: Parental prepregnancy BMI ≥25 kg/m2 is associated with higher incidence of LGA in IVF/ICSI singletons. Paternal prepregnancy BMI ≥25 kg/m2 was likely to have higher risk of birth defect in IVF offspring than those with BMI < 25 kg/m2, particularly in the musculoskeletal system. It is essential for overweight or obesity couples to lose weight before IVF/ICSI treatments.

Regulation of LH secretion by RFRP-3 - From the hypothalamus to the pituitary.

RFamide-related peptides (RFRPs) have long been identified as inhibitors of the hypothalamus-pituitary-gonad axis in mammals. However, less progress has been made in the detailed roles of RFRPs in the control of LH secretion. Recent studies have suggested that RFRP-3 neurons in the hypothalamus can regulate the secretion of LH at different levels, including kisspeptin neurons, GnRH neurons, and the pituitary. Additionally, conflicting results regarding the effects of RFRP-3 on these levels exist. In this review, we collect the latest evidence related to the effects of RFRP-3 neurons in regulating LH secretion by acting on kisspeptin neurons, GnRH neurons, and the pituitary and discuss the potential role of the timely reduction of RFRP-3 signaling in the modulation of the preovulatory LH surge.

Association of serum anti-Müllerian hormone and other factors with cumulative live birth rate following IVF.

RESEARCH QUESTION: What are the optimal values of maternal age and body mass index (BMI), paternal age and BMI, number of oocytes retrieved, and serum AMH concentrations for cumulative live birth rate (CLBR) in IVF and embryo transfer (IVF-ET)? DESIGN: This retrospective cohort study included 9494 women who underwent their first IVF-ET cycle between January 2017 and July 2018. The primary outcome was the CLBR within one complete cycle. Cox regression analysis was used to test the hazard ratio, with 95% confidence intervals. RESULTS: CLBR was significantly lower when maternal age was over 35 (adjusted P < 0.01 for age 36-38 years, adjusted P < 0.00001 for all age groups above 38 years). CBLR increased with increasing serum AMH concentrations and number of retrieved oocytes up to peak values at 5-7 ng/ml AMH and 16-20 oocytes in all women. CLBR was significantly increased when serum AMH concentrations were 3-7 ng/ml (adjusted P < 0.001) and number of oocytes retrieved was more than five (adjusted P < 0.00001). Overweight had a negative effect on CLBR compared with normal BMI in women under 35 years of age (adjusted P = 0.037). In women aged over 35 years, paternal overweight had a negative effect on CLBR compared with normal paternal BMI (adjusted P < 0.01). CONCLUSIONS: Maternal age had an impact on optimal serum AMH concentrations and number of oocytes retrieved. Maternal overweight negatively affected CLBR in women under 35 years of age, and paternal overweight negatively affected CLBR in women over 35 years.

Predictive value of serum kisspeptin concentration at 14 and 21 days after frozen-thawed embryo transfer.

RESEARCH QUESTION: Can serum kisspeptin levels 14 and 21 days after frozen-thawed embryo transfer predict the early pregnancy outcome of patients? DESIGN: Prospective study, with 133 patients undergoing frozen-thawed embryo transfer. Patients were divided into non-pregnant group and pregnant group (including biochemical pregnancy, singleton pregnancy, miscarriage and twin groups). RESULTS: Serum kisspeptin levels on day 21 were significantly higher than day 14 in singleton pregnancy, miscarriage and twin groups (all P < 0.0001), but not in the biochemical pregnancy group. Similarly, serum human chorionic gonadotrophin (HCG) levels were higher on day 21 compared with day 14 except for the biochemical pregnancy group. Compared with the twin group (296.9 pg/ml), the other four groups showed significantly higher serum kisspeptin levels on day 14 (non-pregnant 548.9, biochemical pregnancy 440.4, miscarriage 434.9, singleton pregnancy group 420.9 pg/ml, P < 0.01, P = 0.016, P = 0.034, P = 0.036, respectively). The miscarriage (762.2 pg/ml), singleton pregnancy (730.8 pg/ml) and twin groups (826.3 pg/ml) had significantly higher kisspeptin levels than the biochemical pregnancy group (397.3 pg/ml) on day 21 (P < 0.001, P < 0.01, P < 0.001, respectively). Serum kisspeptin levels on day 14 were negatively correlated with embryo implantation rate (P = 0.035, R2 = -0.880). Serum kisspeptin levels on day 21 have a poor predictive value of miscarriage compared with serum HCG levels (area under the curve = 0.53 and 0.78, respectively). CONCLUSIONS: Serum kisspeptin levels on day 14 are negatively correlated with embryo implantation rate. Serum kisspeptin levels on day 21 have a poor predictive value of miscarriage.

Artificial Sweetener and the Risk of Adverse Pregnancy Outcomes: A Mendelian Randomization Study.

The relationship between the intake of artificial sweetener (AS) and adverse pregnancy outcomes is under-researched, and existing studies yield inconsistent conclusions. A Mendelian randomization (MR) approach was employed to investigate the causal relationship between the intake of AS and adverse pregnancy outcomes. Instrumental variables related to the exposure phenotype were selected for analysis. The analysis was conducted using genome-wide association study summary data from public datasets. The inverse variance weighted, MR-Egger, weighted median, simple mode, and weighted mode methods were used to evaluate the causal relationship between exposure and outcomes. Sensitivity analysis and multivariable Mendelian randomization enrolling body mass index, type 2 diabetes mellitus, and fasting glucose were employed to further validate the consistency and robustness of the results. In univariable MR, the intake of AS added to tea was associated with an increased risk of ectopic pregnancy [OR = 1.821 (1.118-2.967), p = 0.016]. In multivariable MR adjusting for body mass index and type 2 diabetes mellitus, the intake of AS added to cereal was linked to a reduced risk of ectopic pregnancy [OR = 0.361 (0.145-0.895), p = 0.028] and premature rupture of membranes [OR = 0.116 (0.019-0.704), p = 0.019], while the intake of artificial sweetener added to coffee was associated with an increased risk of placenta previa [OR = 1.617 (1.042-2.510), p = 0.032]. No causal relationship was identified between the intake of artificial sweetener and other adverse pregnancy outcomes. The consumption of artificial sweetener during pregnancy warrants careful consideration.

Long-term embryo vitrification is associated with reduced success rates in women undergoing frozen embryo transfer following a failed fresh cycle.

OBJECTIVE: To investigate the association of long-term embryo vitrification with the success rates and neonatal outcomes in frozen cycles. STUDY DESIGN: A single-center, retrospective cohort study was performed in Peking University Third Hospital. We included women who had undergone their first vitrified-warmed cycles following an unsuccessful fresh embryo transfer cycle between January 2013 and December 2019. Restricted cubic splines with 4 knots (at min-3.0 months, 3.1-6.0 months, 6.1-12.0 months, 12.1-max months) were used to map the non-linear relationship between live birth and embryo storage time as a continuous variable after adjustment for covariates. Multiple logistic regression was used to calculate crude odds ratios (OR) and adjusted OR (aOR) with 95 % confidence intervals (CI). RESULTS: A total of 10,167 women undergoing their first frozen cycle following an unsuccessful fresh embryo transfer cycle were included, among whom 3,708 resulted in a live birth (3,254 singleton live births). Restricted cubic splines, both before and after adjusting for covariates, showed that the predicted live birth rate (LBR) progressively decreased with an increase in the duration of embryo cryopreservation. This trend was also evident when women were categorized into four groups based on the length of cryopreservation. The live birth rate (LBR) was highest in the 0.8-3.0 months group (38 %) compared to the other groups. Multivariable logistic regression with the 0.8-3.0 months group as the reference, demonstrated that the 6.1-12.0 months group and >12.0 months group experienced lower live birth rates (aOR = 0.82 (0.72, 0.94) and aOR = 0.71 (0.57, 0.88), respectively). The LBR for the 3.1-6.0 months group was comparable to that of the 0.8-3.0 months group, with an aOR of 0.98 (0.90, 1.07). Sensitivity analyses in women who underwent single blastocyst transfer, in women with at least one good-quality embryo for transfer, and in women with age less than 36 at embryo transfer demonstrated a similar association between LBR and embryo frozen time. The neonatal outcomes were not significantly different among the four groups. CONCLUSIONS: Embryo vitrification greater than six months is associated with a reduction in success rate but does not appear to alter neonatal outcome.

Addition of operative hysteroscopy to vacuum aspiration for the management of early pregnancy loss after in vitro fertilization.

OBJECTIVE: To investigate whether operative hysteroscopy in addition to vacuum aspiration for the management of early pregnancy loss effectively increases the success rate of subsequent frozen embryo transfer. DESIGN: Propensity score-matched cohort study. SETTING: Academic hospital. PATIENT(S): Women with a miscarriage at 5-16 gestational weeks during an in vitro fertilization cycle in Peking University Third Hospital from 2015 to 2022. INTERVENTION(S): Hysteroscopy plus vacuum aspiration vs. conventional vacuum aspiration. MAIN OUTCOME MEASURE(S): Live birth rate in the subsequent frozen embryo transfer. RESULT(S): A total of 347 women who underwent vacuum aspiration plus hysteroscopy and 2,562 women who underwent conventional vacuum aspiration were included in the analysis. After propensity score matching (1:1 ratio), 325 women were included in each group. Compared with women who underwent vacuum aspiration, those who underwent vacuum aspiration plus hysteroscopy were associated with a lower rate of live birth in the propensity score-based matched cohort (22% vs. 30%; adjusted odds ratio, 0.68 [0.47-0.97]). Biochemical, clinical, and multiple pregnancy rates were not significantly different, as was the miscarriage rate. In the overall cohort, 11 women experienced surgery reintervention in the vacuum aspiration group (0.4%), whereas none required surgery reintervention in the vacuum aspiration plus hysteroscopy group. CONCLUSION(S): Women who underwent vacuum aspiration plus hysteroscopy may be associated with lower rates of live birth than those who underwent vacuum aspiration. Further studies are necessary to establish this relationship definitively.

Mechanism of trophoblast cell-derived microparticles mediated immunocontraceptive response.

PROBLEM: Immunomodulation profoundly affects the process of human implantation. Trophoblast cell-derived microparticles (Tr-MPs) may activate specific T cells to attack trophoblast cells, thus potentially acting as an immunocontraceptive vaccine. The safety and persistence of Tr-MP vaccine are needed to address. METHOD OF STUDY: Flow cytometry and confocal fluorescent microscopy were conducted to detect cellular absorptivity and localization of Tr-MPs in bone marrow-derived dendritic cells (BMDCs). The phenotype and cytokine secretion of BMDC and T cells were performed by flow cytometry and enzyme-linked immuno sorbent assay (ELISA). The constructed vaccine female moused model were used to observe the infertile effect and safety of Tr-MPs. RESULTS: As compared with non-irradiation exposure groups, the number of MPs released by trophoblast cells in ultraviolet immunized groups significantly increased. The phagocytosis of Tr-MPs led to the maturation of dendritic cells (DCs), which, in turn, activate T cells. Then cytotoxic T cells attacking trophoblast cells. In mouse model, female mice were infertile after receiving Tr-MPs, and the effect of contraception is transient and safety. CONCLUSION: Using Tr-MPs to initiate an adaptive immune response against alloantigens in trophoblast cells. Tr-MPs may be a new candidate for the development of contraceptive vaccines due to its effectiveness, safety, and reversibility.

A Prediction Model of Gestational Diabetes Mellitus Based on OGTT in Early Pregnancy: A Prospective Cohort Study.

CONTEXT: Gestational diabetes mellitus (GDM) is a common obstetric complication. Although early intervention could prevent the development of GDM, there was no consensus on early identification for women at high risk of GDM. OBJECTIVE: To develop a reliable prediction model of GDM in early pregnancy. METHODS: In this prospective cohort study, between May 30, 2021, and August 13, 2022, a total of 721 women were included from Women's Hospital, Zhejiang University School of Medicine. Participants were asked to complete an oral glucose tolerance test (OGTT) during gestational weeks 7 through 14 for early prediction of GDM, and at weeks 24 through 28 for GDM diagnosis. Using OGTT results and baseline characteristics, logistic regression analysis was used to construct the prediction model. Receiver operating characteristic (ROC) curve, Hosmer-Lemeshow test, decision clinical analysis, and a nomogram were used for model performances assessment and visualization. Internal and external validation was performed to testify the stability of this model. RESULTS: According to the International Association of Diabetes and Pregnancy Study Groups criteria in early OGTT, the mean (SD) age was 30.5 ± 3.7 years in low-risk participants and 31.0 ± 3.9 years in high-risk participants. The area under ROC curve (AUC) of the existing criteria at weeks 7 through 14 varied from 0.705 to 0.724. Based on maternal age, prepregnancy body mass index, and results of early OGTT, the AUC of our prediction model was 0.8720, which was validated by both internal (AUC 0.8541) and external (AUC 0.8241) confirmation. CONCLUSIONS: The existing diagnostic criteria were unsatisfactory for early prediction of GDM. By combining early OGTT, we provided an effective prediction model of GDM in the first trimester.

Primary repair of esophageal atresia gross type C via thoracoscopic magnetic compression anastomosis: A case report.

BACKGROUND: Esophageal atresia (EA) is a life-threatening congenital malformation in newborns, and the traditional repair approaches pose technical challenges and are extremely invasive. Therefore, surgeons have been actively investigating new minimally invasive techniques to address this issue. Magnetic compression anastomosis has been reported in several studies for its potential in repairing EA. In this paper, the primary repair of EA with magnetic compression anastomosis under thoracoscopy was reported. CASE SUMMARY: A full-term male weighing 3500 g was diagnosed with EA gross type C. The magnetic devices used in this procedure consisted of two magnetic rings and several catheters. Tracheoesophageal fistula ligation and two purse strings were performed. The magnetic compression anastomosis was then completed thoracoscopically. After the primary repair, no additional operation was conducted. A patent anastomosis was observed on the 15th day postoperatively, and the magnets were removed on the 23rd day. No leakage existed when the transoral feeding started. CONCLUSION: Thoracoscopic magnetic compression anastomosis may be a promising minimally invasive approach for repairing EA.

Prevention of Gestational Diabetes Mellitus and Gestational Weight Gain Restriction in Overweight/Obese Pregnant Women: A Systematic Review and Network Meta-Analysis.

Background: Overweight/obesity is associated with pregnancy-related disorders, such as gestational diabetes mellitus (GDM) and excessive gestational weight gain (GWG). Although multiple interventions have been proposed to prevent GDM and restrict GWG, our knowledge of their comparative efficacy is limited. Objective: To evaluate the effectiveness and identify the optimal intervention strategy to prevent GDM and restrict GWG among overweight/obese pregnant women. Methods: Randomized controlled trials that recruited overweight/obese pregnant women at <20 gestational week were obtained. Predictive and confidence interval plot and surface under the cumulative ranking (SUCRA) were performed using Stata statistical software to determine and compare the efficacy of interventions (diet, physical activity (PA), diet + PA intervention and medication). Results: 23 studies with a total of 8877 participants were eligible for analysis. Our results indicated that although neither PA, diet + PA, diet nor medication intervention could significantly protect overweight/obese women from the development of GDM, there was a trend that PA and diet + PA intervention were preventive factors of GDM. Of these, PA intervention (SUCRA, 82.8%) ranked as the superior strategy, and diet intervention (SUCRA, 19.7%) was the least efficacious regimen. Furthermore, interventions of diet, PA and diet + PA were significantly beneficial for GWG restriction, whereas medication intervention could not restrict GWG. In detail, diet intervention (SUCRA, 19.7%) ranked as the optimal regimen, whilst PA intervention (SUCRA, 62.3%) ranked as the least efficacious regimen. Conclusion: Although none of the interventions could offer remarkable benefit for GDM prevention, interventions of diet, PA and diet + PA were significant factors to restrict GWG. In aggregate, diet + PA intervention seemed the superior choice for the prevention of both GDM and excessive GWG. Registration: PROSPERO CRD42022313542.