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

BACKGROUND: Cumulative 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. METHODS: This 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. RESULTS: There 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. CONCLUSIONS: In 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.

Uptake of the core outcome set on polycystic ovary syndrome before and after its publication.

STUDY QUESTION: Does the core outcome set (COS) on polycystic ovary syndrome (PCOS) impact the selection of research outcomes? SUMMARY ANSWER: Following the publication of the COS on PCOS, an increasing number of trials are reporting both the generic domain and body mass index; however, the uptake of this COS has not been as extensive as expected. WHAT IS KNOWN ALREADY: The COS on PCOS included 33 core outcomes in the following seven domains: the generic (3), metabolic (8), reproductive (7), pregnancy (10), psychological (3), oncological (1), and long-term (1). This was done to improve consistency in outcome selection and definition. However, thus far, no studies have investigated the effectiveness of this COS in the above-mentioned tasks. STUDY DESIGN, SIZE, DURATION: A methodological study based on the trial registries, including 395 eligible clinical trials registered between 1 January 2018 and 21 September 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 1258 registered clinical studies on PCOS were retrieved from the World Health Organization International Clinical Trials Registry Platform. Of those, 395 were selected according to the inclusion and exclusion criteria, and divided into two groups based on the publication date of the COS on PCOS (4 February 2020): pre-publication and post-publication. The practical uptake of this COS was explored after data collation, assessment, comparison of the uptake of core outcomes or domains before and after the publication of this COS, and correlation analysis between the domains. MAIN RESULTS AND THE ROLE OF CHANCE: There were 26 out of 33 core outcomes and five out of seven domains reported in the 395 trials. The highest uptake was observed for the reproductive domain and the reproductive hormonal profile (63.0% and 38.7%, respectively). After the publication of the COS on PCOS, the uptake of the generic domain and body mass index increased from 24.1% to 35.8% (P = 0.011) and 17.8% to 26.5% (P = 0.039), respectively. The total number of reported core outcomes in the generic domain met statistical significance (P = 0.012). Moreover, multivariable analyses still supported the above finding in the generic domain. Correlation analysis showed that most of the domains were positively correlated with each other. However, the pregnancy domain was negatively correlated with the metabolic domain. Reasons responsible for the unsatisfactory uptake may be the absence of specific definitions of core outcomes, as well as the lack of awareness among researchers regarding this COS. LIMITATIONS, REASONS FOR CAUTION: Due to the lack of standardized definition of outcomes, it was difficult to avoid some subjectivity in the process of consistency assessment. WIDER IMPLICATIONS OF THE FINDINGS: Two years after its publication, there was no substantial improvement in the uptake of the COS on PCOS. This suggests that this COS may require further revision, refinement, and promotion to improve the comparability of PCOS studies. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by Beijing Municipal Health Science and Technology Achievements and Appropriate Technology Promotion Project (BHTPP2022069), and the special fund of Beijing Key Clinical Specialty Construction Project. The authors do not have conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Effects of two different types of luteal support on pregnancy outcomes following antagonist fresh embryo transfer: a retrospective study.

BACKGROUND: Only a small number of studies have reported the use of progesterone vaginal gel in combination with dydrogesterone as part of the antagonist protocol for fresh embryo transfer. Therefore, this study aimed to compare the effects of two types of luteal support on pregnancy outcomes following the antagonist protocol for fresh embryo transfer. METHODS: We performed a retrospective analysis of clinical data from infertile patients who underwent fresh embryo transfer via the antagonist protocol (2785 cycles) between February and July 2019 and between February and July 2021 at the Peking University Third Hospital Reproductive Medicine Centre. According to the luteal support received, the cycle groups were divided into the progesterone vaginal gel group (single medication or VP group; 1170 cycles) and the progesterone vaginal gel plus dydrogesterone group (combination medication or DYD + VP group; 1615 cycles). After propensity score matching, the clinical pregnancy, ongoing pregnancy, early miscarriage, and ectopic pregnancy rates were compared between the two groups. RESULTS: In total, 1057 pairs of cycles were successfully matched via propensity scores. The clinical and ongoing pregnancy rates in the combination medication group were significantly higher than those in the single medication group (P < 0.05), whereas no significant differences were noted in the early miscarriage and ectopic pregnancy rates between the two groups (both P > 0.05). CONCLUSIONS: Combined luteal support after the antagonist protocol is preferred for patients undergoing fresh cycle embryo transfer.

Maternal and neonatal outcomes following blastocyst biopsy for PGT in single vitrified-warmed embryo transfer cycles.

RESEARCH QUESTION: Does blastocyst biopsy for preimplantation genetic testing (PGT) increase the risk of adverse maternal and neonatal outcomes? STUDY DESIGN: Retrospective cohort study of 5097 single vitrified-warmed blastocyst transfer cycles from January 2016 to December 2018, with 2061 cycles in the biopsied group and 3036 cycles in the unbiopsied group enrolled in the analyses. Maternal and neonatal outcomes were compared between the two groups. RESULTS: The live birth rate in the biopsied group (41.1%) was significantly higher than that in the unbiopsied group (35.6%, adjusted odds ratio [aOR] 1.27, 95% confidence interval [CI] 1.05-1.54, P = 0.012) after adjusting for maternal age, maternal body mass index, gravidity, parity, infertility diagnosis, timing of blastocyst transfer, blastocyst quality, regimen of endometrial preparation, endometrial thickness before transfer and treatment year. The rates of total pregnancy loss (25.4% versus 32.2%, aOR 0.69, 95% CI 0.52-0.91, P = 0.008) and early miscarriage (12.1% versus 17.3%, aOR 0.56, 95% CI 0.38-0.83, P = 0.004) were significantly lower in the biopsied group than in the unbiopsied group. No significant differences were found in sex ratio or the risks of hypertensive disorders in pregnancy, diabetes in pregnancy, placenta previa, preterm premature rupture of membranes, low birthweight, very low birthweight, macrosomia, small for gestational age, large for gestational age or birth defects between the two groups. When the subgroup analyses were conducted based on different types of PGT, similar patterns were found for all types. CONCLUSION: Blastocyst biopsy might not increase the risks of adverse maternal and neonatal outcomes in the short term.

Analysis of in vitro fertilization/intracytoplasmic sperm injection outcomes in infertile women with a history of thyroid cancer: a retrospective study.

BACKGROUND: Recent studies have revealed that women with infertility have a higher risk of thyroid cancer (TC) than fertile women. However, studies on whether a history of thyroid cancer affects clinical outcomes in women who conceive using in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) are scarce. We investigate whether a history of thyroid cancer (TC) affects the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes and increases the risk of adverse obstetric outcomes in women with infertility. METHODS: This retrospective study enrolled 384 women with infertility who underwent their first IVF/ICSI treatment at the Peking University Third Hospital between 2010 and 2019. Participants were divided into the TC (64 women with TC history) and control (320 women matched from 85,272 women without thyroid diseases) groups. Controls were individually matched to the TC group according to age, body mass index, concomitant infertility factors, first IVF/ICSI dates, and controlled ovarian stimulation and embryo transfer procedure protocols. IVF/ICSI outcomes, including the numbers of retrieved oocytes and high-grade embryos, clinical pregnancy, miscarriage, preterm delivery, and live birth rates, and adverse obstetric outcome risk were assessed. RESULTS: The TC group had significantly higher thyroid hormone and lower thyroid-stimulating hormone (TSH) levels than the control group. Despite similar gonadotropin treatment dosage, the TC group had a significantly lower numbers of retrieved oocytes and high-grade embryos than the control group. The occurrence rates of clinical pregnancy, miscarriage, preterm delivery, live births, and adverse obstetric outcomes, including multiple gestation, preterm delivery, gestational diabetes mellitus, gestational hypertension, low birth weight, and large-for-gestational-age infants, were not significantly different between the two groups. CONCLUSIONS: TC history did not affect the pregnancy outcomes or increase the risk of adverse obstetric outcomes after the first IVF/ICSI, but it may decrease the number of retrieved oocytes and high-grade embryos.

Acute miliary tuberculosis in pregnancy after in vitro fertilization and embryo transfer: a report of seven cases.

BACKGROUND: While miliary tuberculosis (TB) in pregnancy is rare after in vitro fertilization and embryo transfer (IVF-ET), it poses a serious threat to the health of pregnant women and their fetuses. The present study aimed to describe the clinical features of miliary TB and pregnancy outcomes of patients after IVF-ET. METHODS: Data of infertile patients who received IVF-ET at Peking University Third Hospital between January 2012 and December 2017 were retrospectively analyzed. Patients who developed miliary TB during pregnancy were identified, and clinical characteristics of miliary TB were described. RESULTS: Out of 62,755 infertile women enrolled, 7137 (11.4 %) showed signs of prior pulmonary TB on chest X-ray (CXR). Among the 15,136 women (mean age: 33.2 ± 5.0 years) who successfully achieved clinical pregnancy, seven patients aged 28-35 years had miliary TB during pregnancy, with two patients having a complication of TB meningitis. All these patients presented with fever. Notably, old TB lesions were detected on CXR in six patients before IVF-ET; nevertheless, no anti-TB therapy was administered. Furthermore, salpingography revealed oviduct obstruction in all patients (7/7). Patients received anti-TB therapy following a diagnosis of miliary TB and were clinically cured. However, pregnancy was terminated due to spontaneous (4/7) and induced (3/7) abortion. CONCLUSIONS: TB reactivation, mostly as miliary TB and TB meningitis, is severe in pregnant women after IVF-ET and deleterious to pregnancy outcomes. Signs of prior TB on CXR may be risk factors for TB reactivation during pregnancy.

Impact of thyroid cancer treatment on assisted reproductive technology outcomes in women with infertility.

PURPOSE: We investigated the effect of different surgical procedures and radioactive iodine treatment (RAIT) on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes and evaluated whether possible risk factors, including age, thyroid-stimulating hormone (TSH) levels, and thyroid antibody positivity, were associated with adverse IVF/ICSI outcomes. METHODS: This retrospective study included 76 women with infertility who had received thyroid cancer (TC) treatment among 137,698 infertile women who underwent IVF/ICSI cycles at the Peking University Third Hospital between 2010 and 2019. Clinical pregnancy and live birth rates were assessed. RESULTS: We found that the clinical pregnancy and live birth rates in women who underwent partial thyroidectomy were 7- and 6-fold higher, respectively, than those in women who underwent total thyroidectomy. We observed no significant differences in the clinical pregnancy and live birth rates between the RAIT and non-RAIT groups, even after adjusting for age, TSH levels, surgical treatment, and thyroid antibody positivity. Multivariate logistic regression analysis showed that age and TSH levels were not associated with decreased clinical pregnancy and live birth rates. Women with thyroid antibody positivity had significantly lower clinical pregnancy and live birth rates than women without thyroid antibody positivity. CONCLUSION: Our study showed lower clinical pregnancy and live birth rates in women who underwent total thyroidectomy than in women who underwent partial thyroidectomy. Thyroid antibody positivity is an important risk factor for adverse IVF/ICSI outcomes in women who have received TC treatment.

Effect of Levothyroxine on Miscarriage Among Women With Normal Thyroid Function and Thyroid Autoimmunity Undergoing In Vitro Fertilization and Embryo Transfer: A Randomized Clinical Trial.

Importance: Presence of thyroid autoantibodies in women with normal thyroid function is associated with increased risk of miscarriage. Whether levothyroxine treatment improves pregnancy outcomes among women undergoing in vitro fertilization and embryo transfer (IVF-ET) is unknown. Objective: To determine the effect of levothyroxine on miscarriage among women undergoing IVF-ET who had normal thyroid function and tested positive for thyroid autoantibodies. Design, Setting, and Participants: An open-label, randomized clinical trial involving 600 women who tested positive for the antithyroperoxidase antibody and were being treated for infertility at Peking University Third Hospital from September 2012 to March 2017. Interventions: The intervention group (n = 300) received either a 25-µg/d or 50-µg/d dose of levothyroxine at study initiation that was titrated according to the level of thyroid-stimulating hormone during pregnancy. The women in the control group (n = 300) did not receive levothyroxine. All participants received the same IVF-ET and follow-up protocols. Main Outcomes and Measures: The primary outcome was the miscarriage rate (pregnancy loss before 28 weeks of gestation, which was calculated among women who became pregnant). The secondary outcomes were clinical intrauterine pregnancy rate (fetal cardiac activity seen at sonography observation on the 30th day after the embryo transfer), and live-birth rate (at least 1 live birth after 28 weeks of gestation). Results: Among the 600 women (mean [SD] age, 31.6 [3.8] years) randomized in this trial, 567 women (94.5%) underwent IVF-ET and 565 (94.2%) completed the study. Miscarriage rates were 10.3% (11 of 107) in the intervention group and 10.6% (12 of 113) in the control group, with the absolute rate difference (RD) of -0.34% (95% CI, -8.65% to 8.12%) over the 4.5-year study period. Clinical intrauterine pregnancy rates were 35.7% (107 of 300) in the intervention group and 37.7% (113 of 300) in the control group, with an absolute RD of -2.00% (95% CI, -9.65% to 5.69%). Live-birth rates were 31.7% (95 of 300) in the intervention group and 32.3% (97 of 300) in the control group, with an absolute RD of -0.67% (95% CI, -8.09% to 6.77%). Conclusions and Relevance: Among women in China who had intact thyroid function and tested positive for antithyroperoxidase antibodies and were undergoing IVF-ET, treatment with levothyroxine, compared with no levothyroxine treatment, did not reduce miscarriage rates or increase live-birth rates. Trial Registration: Chinese Clinical Trial Registry: ChiCTR-TRC-13004097.

[Impact of different luteal support methods on clinical outcomes of frozen-thawed embryo transfer cycles].

OBJECTIVE: To determine whether luteal support of dydrogesterone may enhance the outcome of frozen-thawed embryo transfer (FET) in natural cycles by comparing the FET outcomes of different luteal support methods. METHODS: A total of 2 248 natural FET cycles with an endometrial thickness of 8-12 mm and type A on ovulation day, from January 2011 to March 2013 were chosen. Oral dydrogesterone (n = 1 967) or intramuscular progesterone (n = 281) was used for luteal support. The rates of clinical pregnancy, implantation, ectopic pregnancy, miscarriage and live birth were compared among these groups. RESULTS: The patients receiving oral dydrogesterone or intramuscular progesterone had similar profiles of age, type of infertility, endometrial thickness and average numbers of embryo transfer. The dydrogesterone group had higher rates of clinical pregnancy (43.26% vs 38.79%) and implantation (25.76% vs 21.13%). However a lower miscarriage rate (17.27% vs 22.02%) was insignificant. The rates of ectopic pregnancy, premature birth and live birth were also similar. When infertile factors were considered, the dydrogesterone group had significantly higher clinical pregnancy rates (43.78% vs 34.38%, P < 0.05), lowered miscarriage rates (16.54% vs 29.55%, P < 0.05) and increased live birth rates (34.16% vs 23.44%, P < 0.05) among simple tubal factor patients. CONCLUSION: Oral administration of dydrogesterone for luteal support offers more advantages in natural cycle FET than intramuscular progesterone, especially for simple tubal factor infertility.

Intracytoplasmic Sperm Injection Versus In vitro Fertilization in Infertile Women with Thyroid Autoimmunity.

Background: It has been reported that intracytoplasmic sperm injection (ICSI) may be the preferred fertilization method for women with thyroid autoimmunity (TAI) seeking assisted reproduction. We compared the reproductive outcomes of women with TAI who were treated with ICSI compared with in vitro fertilization (IVF). Methods: In this retrospective cohort study, we included women with infertility who were referred to the Reproductive Centre of Peking University Third Hospital for their first IVF/ICSI and embryo transfer (ET) treatment cycle from January 2019 to February 2021. In total, 2171 and 743 women with TAI underwent IVF and ICSI, respectively, while 8702 and 2668 women without TAI underwent IVF and ICSI, respectively. We examined the cumulative live birth rate (primary outcome) from the initiated stimulative cycle as well as the secondary outcomes of fertilization rate, rates of clinical pregnancy, and live birth after the first ET cycle. We compared the reproductive outcomes of women treated with IVF and ICSI according to TAI status. Multivariable logistic regression analyses were performed to adjust for relevant confounders. Results: Women who underwent ICSI had significantly higher fertilization rates than those who underwent IVF (median [interquartile range]: 0.6 [0.5-0.8] in the TAI-positive and IVF group vs. 0.7 [0.5-0.8] in the TAI-positive and ICSI group vs. 0.6 [0.5-0.8] the TAI-negative and IVF group vs. 0.7 [0.5-0.8] in the TAI-negative and ICSI group, p < 0.001). However, the rates of cumulative live births, clinical pregnancies, and live births were significantly lower among women with TAI who underwent ICSI than those who underwent IVF (cumulative live birth: 51.8% vs. 47%, adjusted odds ratio [aOR]: 0.80 [confidence interval, CI: 0.67-0.97]; clinical pregnancy: 43.0% vs. 38.8%, aOR: 0.81 [CI: 0.67-0.97]; live birth: 36.2% vs. 32.4%, aOR: 0.81 [CI: 0.66-0.98]). Conclusion: We observed that the use of ICSI in women with TAI was not associated with better assisted reproductive outcomes compared with IVF. Further prospective clinical trials are needed to confirm our findings.

Direct visual observation of pedal motion-dependent flexibility of single covalent organic frameworks.

Flexible covalent organic frameworks (COFs) have been studied for applications containing sorption, selective separation, and catalysis. How to correlate the microscopic structure with flexibility in COFs is a great challenge. Herein, we visually track the flexible deformation behaviors of single COF-300 and COF-300-AR particles in response to solvent vapour guests with dark-field microscopy (DFM) in an in operando manner. COF-300-AR with freely-rotating C-N single bonds are synthesized by the reduction of imine-based COF-300 consisting of rigid C=N double bonds without changing topological structure and crystallinity. Unexpectedly, we observe that the flexible deformation of COF-300 is extremely higher than that of COF-300-AR despite it bears many C-N single bonds, clearly illustrating the apparent flexibility decrease of COF-300 after reduction. The high spatiotemporal resolution of DFM enables the finding of inter-particle variations of the flexibility among COF-300 crystals. Experimental characterizations by variable-temperature X-ray diffraction and infrared spectroscopy as well as theoretical calculations demonstrate that the flexible deformation of COF-300 is ascribed to the pedal motion around rigid C=N double bonds. These observations provide new insights into COF flexibility.

Impact of thyroid-stimulating hormone levels after controlled ovarian hyperstimulation on in vitro fertilization/intracytoplasmic sperm injection outcomes in women with fresh embryo transfer: a prospective cohort study.

Objective: Maternal hypothyroidism before and during pregnancy is associated with an increased risk of adverse pregnancy outcomes; many studies have evidenced that controlled ovarian hyperstimulation (COH) triggers a significant increase in the levels of TSH; however, no large-scale prospective studies have evaluated the impact of TSH levels after COH on assisted reproductive technology outcomes. The aim of this prospective study was to investigate whether in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes are affected by TSH levels after COH in women with fresh embryo transfer (ET). Methods: A total of 664 patients who underwent IVF/ICSI treatment and received fresh ET at the Peking University Third Hospital were included in this study. The rates of clinical pregnancy, miscarriage, live birth, and preterm delivery were analyzed. Results: The patients were categorized into two groups based on serum TSH levels after COH (0.55 mIU/L < TSH < 2.5 mIU/L: n= 449, 2.5 mIU/L ≤ TSH ≤ 4.78 mIU/L: n= 215). There were no significant differences in the rates of clinical pregnancy, miscarriage, and live birth between the two groups, even after adjusting for age, body mass index (BMI), thyroid antibody positivity, and COH protocols. However, the preterm delivery rate was significantly higher in women with TSH < 2.5 mIU/L than in those with TSH ≥ 2.5 mIU/L, even after adjusting for relevant confounding factors. There was no significant difference in live birth weight between the two groups. Discussion: Mildly elevated TSH levels (TSH ≥ 2.5 mIU/L) after COH did not affect IVF/ICSI outcomes, and strict control of TSH levels within 2.5 mIU/L after COH might not be necessary. Additionally, strictly controlled TSH levels (TSH < 2.5 mIU/L) may increase preterm delivery risk.

Impact of thyroid autoimmunity and vitamin D on in vitro fertilization/intracytoplasmic sperm injection outcomes among women with normal thyroid function.

This prospective cohort study aimed to determine the impact of thyroid autoimmunity and total 25-hydroxyvitamin D concentration on early pregnancy outcomes in women undergoing in vitro fertilization/intracytoplasmic sperm injection who had intact thyroid function. The study included 1,297 women who underwent in vitro fertilization/intracytoplasmic sperm injection cycles, although only 588 patients received fresh embryo transfer. The study endpoints were clinical pregnancy, ongoing pregnancy, ectopic pregnancy, and early miscarriage rates. Our study found that the total 25-hydroxyvitamin D serum concentrations (P<0.001) and anti-Mullerian hormone levels (P=0.019) were lower among patients in the TAI group (n=518) than among those in the non-TAI group (n=779). Additionally, the study population in each group was divided into three subgroups according to the total vitamin D status based on clinical practice guidelines (deficient, <20 ng/mL; insufficient, 21-29 ng/mL; and sufficient, ≥30 ng/mL), TAI group: sufficient, n=144; insufficient, n=187; and deficient, n=187; non-TAI group: sufficient, n=329; insufficient, n=318, and deficient, n=133. In the TAI group, the number of good-quality embryos decreased in patients with vitamin D deficiency (P=0.007). Logistic regression analysis indicated that aging prevented women from achieving clinical (P=0.024) and ongoing pregnancy (P=0.026). The current findings suggest that patients with TAI had reduced serum vitamin D concentration. Furthermore, in the TAI group, the number of good-quality embryos decreased in patients with vitamin D deficiency. Finally, aging adversely impacted achieving clinical and ongoing pregnancy.

Maternal preconception thyroid autoimmunity is associated with neonatal birth weight conceived by PCOS women undergoing their first in vitro fertilization/intracytoplasmic sperm injection.

BACKGROUND: Thyroid autoimmunity and polycystic ovary syndrome (PCOS) are the most common endocrinopathies and have close relationships based on common etiology and pathogenesis, including genetic susceptibility, metabolic disorders, hormonal dysregulation, immune response, and inflammatory activation. The co-occurrence of both diseases is associated with adverse reproductive outcomes, but its effect on neonatal outcomes remains largely unknown. We aim to explore the effect of thyroid autoimmunity on neonatal birth weight in PCOS women undergoing IVF/ICSI. METHODS: This is a retrospective analysis of 486 PCOS women who underwent the first IVF/ICSI cycles and gave birth to 361 singletons and 125 twins during 2018 - 2020 at a reproductive center. The associations between maternal preconception serum thyroid function and autoimmunity indicators and birth weights of the singleton and twin groups were evaluated using generalized linear models (GLMs) and generalized estimate equations (GEEs), respectively. Analyses were further stratified by neonatal sex, maternal age, and maternal preconception BMI to assess the possible interaction effects. RESULTS: Maternal preconception serum TPOAb had a significant negative association with singleton birth weight (P for trends = 0.03). Compared with women in the first tertile of TPOAb, women in the third tertile had a change in singleton birth weight of - 119.72 g (95% CI: - 222.68 g, - 16.70 g). Maternal preconception serum TPOAb had a significant positive association with twin birth weight (P for trends = 0.01). Compared with women in the first tertile of TPOAb, women in the third tertile had a change in twin birth weight of 138.62 g (95% CI: 33.96 g, 243.30 g). Besides, maternal preconception serum TPOAb had a specific association with increased twin birth weight for female neonates, a specific association with decreased singleton birth weight for PCOS women under 35 years, and a specific association with decreased twin birth weight for overweight PCOS women (all P for interactions < 0.05). CONCLUSIONS: Maternal preconception thyroid autoimmunity may affect the birth weights of both singleton and twin neonates. Further large cohorts and experimental studies are required to confirm these findings and explore the underlying mechanisms.

Adiposity and lipid metabolism indicators mediate the adverse effect of glucose metabolism indicators on oogenesis and embryogenesis in PCOS women undergoing IVF/ICSI cycles.

BACKGROUND: Polycystic ovary syndrome (PCOS) women have high incidences of dyslipidemia, obesity, impaired glucose tolerance (IGT), diabetes, and insulin resistance (IR) and are fragile to female infertility. Obesity and dyslipidemia may be the intermediate biological mechanism for the associations between glucose metabolism dysfunction and abnormal oogenesis and embryogenesis. METHODS: This retrospective cohort study was performed at a university-affiliated reproductive center. A total of 917 PCOS women aged between 20 and 45 undergoing their first IVF/ICSI embryo transfer cycles from January 2018 to December 2020 were involved. Associations between glucose metabolism indicators, adiposity and lipid metabolism indicators, and IVF/ICSI outcomes were explored using multivariable generalized linear models. Mediation analyses were further performed to examine the potential mediation role of adiposity and lipid metabolism indicators. RESULTS: Significant dose-dependent relationships were found between glucose metabolism indicators and IVF/ICSI early reproductive outcomes and between glucose metabolism indicators and adiposity and lipid metabolism indicators (all P < 0.05). Also, we found significant dose-dependent relationships between adiposity and lipid metabolism indicators and IVF/ICSI early reproductive outcomes (all P < 0.05). The mediation analysis indicated that elevated FPG, 2hPG, FPI, 2hPI, HbA1c, and HOMA2-IR were significantly associated with decreased retrieved oocyte count, MII oocyte count, normally fertilized zygote count, normally cleaved embryo count, high-quality embryo count, or blastocyst formation count after controlling for adiposity and lipid metabolism indicators. Serum TG mediated 6.0-31.0% of the associations; serum TC mediated 6.1-10.8% of the associations; serum HDL-C mediated 9.4-43.6% of the associations; serum LDL-C mediated 4.2-18.2% of the associations; and BMI mediated 26.7-97.7% of the associations. CONCLUSIONS: Adiposity and lipid metabolism indicators (i.e., serum TG, serum TC, serum HDL-C, serum LDL-C, and BMI) are significant mediators of the effect of glucose metabolism indicators on IVF/ICSI early reproductive outcomes in PCOS women, indicating the importance of preconception glucose and lipid management and the dynamic equilibrium of glucose and lipid metabolism in PCOS women.

Inflammation mediates the effect of adiposity and lipid metabolism indicators on the embryogenesis of PCOS women undergoing in vitro fertilization/intracytoplasmic sperm injection.

Background: Polycystic ovary syndrome (PCOS) is a complex reproductive endocrine and metabolic disease affecting women of reproductive age. The low-grade chronic inflammation in PCOS is considered to be associated with obesity and dyslipidemia. We aim to investigate the potential mediating role of white blood cell (WBC) count, a representative inflammatory marker, in the effect of adiposity and lipid metabolism indicators on IVF/ICSI outcomes in PCOS women. Methods: We conducted a retrospective cohort study of 1,534 PCOS women who underwent their first IVF/ICSI cycles with autologous oocytes at a reproductive center from January 2018 to December 2020. The associations between PCOS women's adiposity and lipid metabolism indicators and WBC count and IVF/ICSI outcomes were examined using multivariable generalized linear models. Mediation analyses were conducted to evaluate the possible mediating role of WBC count. Results: We found significant dose-dependent correlations between adiposity and lipid metabolism indicators and IVF/ICSI outcomes (i.e., hormone levels on the ovulatory triggering day, oocyte development outcomes, fertilization, early embryo development outcomes, and pregnancy outcomes) (all p < 0.05), as well as between adiposity and lipid metabolism indicators and WBC count (all p < 0.001). Increasing WBC count was associated with adverse oocyte and embryonic development outcomes (all p < 0.05). Mediation analyses suggested that increasing serum TG and LDL-C levels and decreasing serum HDL-C level were significantly associated with reduced high-quality Day 3 embryo count in PCOS women, with 21.51%, 9.75%, and 14.10% mediated by WBC count, respectively (all p < 0.05). Conclusions: We observed significant associations between lipid metabolism indicators and high-quality Day 3 embryo count in PCOS women, partially mediated by inflammation-related mechanisms, suggesting the potential intervention target for improving embryo quality in PCOS women.

Maternal Preconception Glucose Homeostasis and Insulin Resistance Are Associated with Singleton and Twin Birthweight of Neonates Conceived by PCOS Women Undergoing IVF/ICSI Cycles.

Polycystic ovary syndrome (PCOS) can induce fertility and metabolism disorders, which may increase the prevalence of glucose metabolism disorders and cause health hazards to women and their offspring. We aim to evaluate the effect of maternal preconception glucose metabolism on neonatal birthweight in PCOS women undergoing IVF/ICSI cycles. We retrospectively analyzed 269 PCOS women who delivered 190 singletons and 79 twins via IVF/ICSI at a reproductive center. The effects of maternal preconception glucose metabolism indicators on singleton and twin birthweight were evaluated using generalized linear models and generalized estimate equations, respectively. The potential nonlinear associations were evaluated using generalized additive models. The analyses were further stratified by maternal preconception BMI and delivery mode to evaluate the possible interaction effects. Among PCOS women, maternal preconception fasting plasma glucose (FPG) and glycohemoglobin (HbA1c) had significant negative associations with singleton birthweight (all p for trends = 0.04). We also found an overweight-specific association between elevated maternal preconception 2 h plasma insulin (2hPI) and twin birthweight (p for interactions = 0.05) and a caesarean-specific association between maternal preconception HbA1c and singleton birthweight (p for interactions = 0.02) in PCOS women. Maternal preconception glucose metabolism may affect neonatal birthweight, suggesting the importance of preconception glucose and insulin management for PCOS women. Further large prospective cohorts and animal studies are needed to confirm these findings and investigate the potential mechanisms.

Thyroid autoimmunity and vitamin D: Effects on in vitro fertilization/intracytoplasmic sperm injection laboratory outcomes.

This prospective cohort study aimed to determine the effects of thyroid autoimmunity, serum/follicular fluid vitamin D levels, and vitamin D receptor expression in granulosa cells on laboratory outcomes of in vitro fertilization/intracytoplasmic sperm injection. The study included 206 women with or without thyroid autoimmunity undergoing in vitro fertilization/intracytoplasmic sperm injection ovarian stimulation cycles. The primary outcomes in thyroid autoimmunity and non-thyroid autoimmunity patients with high or low follicular fluid vitamin D levels (high vitamin D level, ≥20 ng/mL; low vitamin D level, <20 ng/mL) were the number of oocytes retrieved and quality of embryos. The secondary outcomes were the association between serum and follicular fluid vitamin D levels and vitamin D receptor expression in granulosa cells. Our study revealed that thyroid autoimmunity was associated with fewer good-quality embryos but not oocytes (p = 0.010). The vitamin D level in the follicular fluid was significantly correlated with that in the serum (p < 0.001, r > 0.5). The study populations in the thyroid autoimmunity and non-thyroid autoimmunity groups were divided into two subgroups based on high/low serum/follicular fluid vitamin D levels. There was no significant difference in the number of retrieved oocytes and good-quality embryos between the subgroups with high or low vitamin D levels (p > 0.05), and the incidence of thyroid autoimmunity was comparable between the subgroups (p > 0.05). Linear regression analysis indicated that thyroid autoimmunity had a negative effect on the number of healthy embryos (p = 0.038). Reverse transcription-polymerase chain reaction results indicated that vitamin D receptor expression in granulosa cells was positively correlated with follicular vitamin D levels in the thyroid autoimmunity (p = 0.0002) and non-thyroid autoimmunity (p < 0.0001) groups. The current findings suggest that thyroid autoimmunity may have a more detrimental effect on in vitro fertilization/intracytoplasmic sperm injection laboratory outcomes than vitamin D.

Prognosis of Congenital Anomalies in Conceptions Following In Vitro Fertilization: A Multicenter Retrospective Cohort Study in China.

Background: Conceptions following in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) have an increased risk of congenital anomalies. Few studies have explored the prognosis of fetuses with congenital anomalies. This study aimed to investigate the prevalence and prognosis of congenital anomalies in IVF/ICSI pregnancies, and to analyze the influencing factors contributing to poor prognosis. Methods: In this multicenter retrospective cohort study, we followed 405,473 embryo transfer cycles at 15 reproductive centers between January 2010 and December 2019 and enrolled 2,006 intrauterine pregnancies with congenital anomalies. The relatively positive prognosis group with one or more live births and neonatal survival for more than 7 days was compared with the poor prognosis group with poorer outcomes. Results: Among the 168,270 ongoing intrauterine pregnancy cycles, the prevalence of congenital anomalies was 1.19%, wherein the malformation rates of cycles with late abortion and delivery were 2.37% (716/30,202) and 0.93% (1,290/138,068), respectively. Among all IVF/ICSI cycles with congenital anomalies, the relatively positive prognosis rate was 61.39%. Moreover, the fertilization failure rate (2 pro-nuclei rate < 25%) in the poor prognosis group was significantly higher than that in the relatively positive prognosis group (10.89% vs. 5.09%, p < 0.001). Multivariate logistic regression analysis revealed no significant differences in the relatively positive prognosis rate among the various IVF/ICSI protocols. The relatively positive prognosis rate of fertilization failure cycles was 0.180 times that of normal fertilization cycles. Conclusion: Poor fertilization rates during IVF/ICSI treatments are more likely to have poor prognosis in fetuses or neonates with congenital anomalies, and obstetric management should be strengthened in pregnant women, with which pregnant women should be recommended to strengthen obstetric management.

Immunological Microenvironment Alterations in Follicles of Patients With Autoimmune Thyroiditis.

Autoimmune thyroiditis (AIT) is the most prevalent autoimmune endocrine disease, with a higher incidence in women than in men. Immunological abnormalities may lead to the impairment of ovarian folliculogenesis; however, whether the presence of AIT affects immunological microenvironment in follicles remains controversial. We performed a cross-sectional study including 122 patients, aged 20-40 years, who underwent IVF/ICSI treatment owing to isolated male or tube factor infertility. Patients were divided into AIT and control groups according to clinical presentation, thyroid function, and thyroid autoantibody measurements. Follicular fluid was collected and the distribution of cytokines/chemokines in follicular fluid was measured by flow cytometry using multiplex bead assays between the two groups. Based on differences in levels of intrafollicular chemokines and cytokines between the AIT and control groups, the relevant inflammatory cascade was further demonstrated. Among the 12 chemokines analyzed, three (CXCL9, CXCL10, and CXCL11) showed significantly elevated levels in the follicular fluid of patients with AIT. Among the 11 cytokines detected, compared with those in the control group, significantly higher levels of IFNγ were observed in patients with AIT. IFNγ dose-dependently stimulated the expression and secretion of CXCL9/10/11 in cultured primary granulosa cells. The percentage of CXCR3+ T lymphocytes was significantly elevated in the follicular microenvironment of patients with AIT. We concluded that the IFNγ-CXCL9/10/11-CXCR3+ T lymphocyte inflammatory cascade is activated in the follicular microenvironment of patients with AIT. These findings indicate that a considerable immune imbalance occurred in the follicular microenvironment of patients with AIT.