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.

An Altered Microbiota in the Lower and Upper Female Reproductive Tract of Women with Recurrent Spontaneous Abortion.

Recurrent spontaneous abortion (RSA) is a complex multifactorial disease. Recently, the microbiota of the female reproductive tract, as an emerging factor in RSA, has gradually attracted the attention of many clinical researchers. Here, we reported that the microbiota of the lower and upper female reproductive tracts from patients with RSA showed no significant differences in alpha diversity compared to that of controls. Beta diversity was significantly higher in the RSA group than in the control group in the vaginal microbiota (P = 0.036), cervical microbiota (P = 0.010) and microbiota from uterine lavage fluid (P = 0.001). In addition, dramatic decreases in gamma interferon and interleukin-6 cytokine levels were observed in the RSA group. In conclusion, our data suggested altered microbial biodiversity in the vagina, cervix and uterine lavage fluid in the RSA group. Alterations in the microbiota in the uterine cavity could be associated with altered cytokine levels, which might be a risk factor for RSA pathogenesis. Moreover, the microbiota composition differed markedly from the lower genital tract to the uterine cavity, and the microbiota in the uterine cavity also distinctly varied between endometrial tissue and uterine lavage fluid in the RSA group. Hence, sampling with these two methods simultaneously allowed a more comprehensive perspective of microbial colonization in the uterine cavity. IMPORTANCE As an obstacle to pregnancy, recurrent spontaneous abortion (RSA) can be caused by a variety of factors, and a current understanding of the etiology of RSA is still lacking; half of cases have an unknown cause. A substantial fraction of patients show no improvement after treatment. Since the microbiota of the female reproductive tract has been proposed as an emerging factor in RSA patients, further investigation is needed to provide guidance for clinical therapy. In general, this is the first report describing the distinct alterations of the vaginal, cervical, and uterine microbiota in RSA, not just that in the vagina. Furthermore, another major strength of this study derived from the further in-depth investigation and analysis of the characteristics of the microbiota colonizing the upper female genital tract in RSA, which provided a more comprehensive view for investigating the uterine microbiota.

Efficacy and safety of autologous adipose tissue-derived stromal vascular fraction in patients with thin endometrium: a protocol for a single-centre, longitudinal, prospective self-control study.

INTRODUCTION: Endometrial thickness is an important parameter to evaluate endometrial receptivity. An appropriate endometrial thickness is necessary for both embryo implantation and maintaining normal pregnancy. Women with thin endometrium are one of the critical challenges in the clinic, and current therapeutic strategies for thin endometrium remain suboptimal. The stromal vascular fraction (SVF) derived from adipose tissue contains a variety of cells, mainly adipose-derived stem/stromal cells and adipose cells. Recently, adipose tissue-derived SVF showed tremendous potential for treating thin endometrium due to its capacity to repair and regenerate tissues. The application of SVF in animal models for treating thin endometrium has been investigated. However, limited evidence has demonstrated the efficacy and safety of autologous SVF in patients with thin endometrium. METHODS AND ANALYSIS: This study is a single-centre, longitudinal, prospective self-control study to investigate the preliminary efficacy and safety of autologous SVF in improving the pregnancy outcome of infertile patients with thin endometrium. Thirty patients diagnosed with thin endometrium will be recruited based on the inclusion and exclusion criteria. The SVF suspension will be transferred into the uterine cavity via an embryo transfer catheter. Then, comparisons between pretreatment and post-treatment will be analysed, and the outcomes, including endometrial thickness, menstrual volume and duration, frequency and severity of adverse events and early pregnancy outcomes, will be measured within a 3-month follow-up, while late pregnancy outcomes and their offspring will be followed up via telephone for 2 years. The proportion of patients with improved symptoms will be calculated and compared. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of Peking University Third Hospital (reference number: REC2020-165). Written informed consent will be provided for patients before being included. The results will be presented at academic conferences and a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2000035126.

Effects of Growth Hormone Supplementation on Poor Ovarian Responders in Assisted Reproductive Technology: a Systematic Review and Meta-analysis.

To investigate whether additional growth hormone (GH) treatment can improve pregnancy outcomes in poor ovarian responders (POR), this systematic review and meta-analysis is prospectively designed and has been registered in PROSPERO (Registration number: CRD42019137866). Literature search was conducted in PubMed, EMBASE, Web of Science, and Cochrane Library from January 2010 to June 2019, and studies before 2010 were included based on a Cochrane review published in 2010. Only English articles and randomized clinical trial studies were included. A total of 12 studies were included for analysis. GH treatment in poor ovarian responders significantly increased the clinical pregnancy rate (odds ratio (OR) = 1.75 (1.23, 2.50)), and the live birth rate also tended to increase after GH treatment (OR = 1.51 (0.97, 2.35)). Other outcomes including the gonadotropin requirement, oocyte retrieval number, endometrium thickness, and the number of patients with available embryos for transfer were also improved by growth hormone treatment (weighted mean differences (WMD) = - 0.78 (- 1.23, - 0.33), 1.41 (0.72, 2.09), 0.36 (0.18, 0.53), OR = 2.67 (1.47, 4.68), respectively). Based on the current study, GH treatment in POR can increase clinical pregnancy rate and show a higher but not statistically significant likelihood of live birth rate. The effect is likely to be mediated by improving ovarian response and endometrium thickness. The effect of GH treatment on live birth rate should be tested by further studies with a larger sample size.

Vitamin D supplementation prior to in vitro fertilisation in women with polycystic ovary syndrome: a protocol of a multicentre randomised, double-blind, placebo-controlled clinical trial.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is one of the leading causes of female infertility, affecting around 5% of women of childbearing age in China. Vitamin D insufficiency is common in women with PCOS and is associated with lower live birth rates. However, evidence regarding the effectiveness of vitamin D supplementation in women with PCOS is inconclusive. This multicentre randomised, double-blinded, placebo-controlled trial aims to evaluate the effectiveness of vitamin D supplementation prior to in vitro fertilisation (IVF) on the live birth rate in women with PCOS. METHODS AND ANALYSIS: We plan to enrol women with PCOS scheduled for IVF. After informed consent, eligible participants will be randomised in a 1:1 ratio to receive oral capsules of 4000 IU vitamin D per day or placebo for around 12 weeks until the day of triggering. All IVF procedures will be carried out routinely in each centre. The primary outcome is live birth after the first embryo transfer. The primary analysis will be by intention-to-treat analysis. To demonstrate or refute that treatment with vitamin D results in a 10% higher live birth rate than treatment with placebo, we need to recruit 860 women (48% vs 38% difference, anticipating 10% loss to follow-up and non-compliance, significance level 0.05 and power 80%). ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee in Women's Hospital of Zhejiang University on 2 March 2020 (reference number: IRB-20200035-R). All participants will provide written informed consent before randomisation. The results of the study will be submitted to scientific conferences and a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04082650.

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.

The Potential Role of Growth Hormone on the Endometrium in Assisted Reproductive Technology.

Growth hormone (GH) has been considered as an adjuvant treatment in human assisted reproductive technology (ART) for several years. Its action was largely attributed to an improvement of ovarian function and less emphasis was paid to its role in the uterus. However, there is increasing evidence that GH and its receptors are expressed and have actions in the endometrium and may play an important role in modifying endometrial receptivity. Thus, in this review, we firstly describe the existence of GH receptors in endometrium and then summarize the effects of GH on the endometrium in clinical situations and the underlying mechanisms of GH in the regulation of endometrial receptivity. Finally, we briefly review the potential risks of GH in ART and consider rationalized use of GH treatment in ART.

High antimüllerian hormone levels are associated with preterm delivery in patients with polycystic ovary syndrome.

CONTEXT: Antimüllerian hormone (AMH) levels are higher in patients with polycystic ovary syndrome (PCOS). Accumulating evidence indicates that AMH has an impact on the physiology of the female reproductive system. OBJECTIVE: To investigate the association of AMH levels with the risk of preterm delivery in PCOS patients. DESIGN: Retrospective cohort study. SETTING: Academic fertility center. PATIENTS: Women who underwent in vitro fertilization between January 2017 and July 2018 (25,165 cycles). INTERVENTIONS: None. MAIN OUTCOME MEASURES: The primary outcome was preterm delivery. RESULTS: Serum AMH levels were not different between the term delivery and preterm delivery groups in the entire cohort (3.8 vs. 4.1 ng/mL, P>.05). In patients diagnosed with PCOS, those with preterm delivery had higher AMH levels than were found in patients with term delivery (9.3 vs. 6.9 ng/mL, P<.01). Preterm deliveries predominated in PCOS patients with AMH levels above the 75th percentile (9.75 ng/mL) (adjusted P<.0001, adjusted odds ratio [OR] 4.0, 95% confidence interval [CI] 1.94, 8.08)) and frozen-thawed embryo transfer (FET) patients with AMH levels higher than the 90th percentile (10.10 ng/mL) (adjusted P<.05, adjusted OR 2.0, 95% CI 1.16, 3.36). CONCLUSION: Serum AMH levels higher than 75th percentile were associated with an increased risk of preterm delivery in patients with PCOS, and serum AMH levels higher than the 90th percentile were associated with an increased risk of preterm delivery in FET patients.