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Although periconception vaccination is important to maternal and neonatal health, little is known about the COVID-19 vaccine hesitancy among infertile couples seeking fertility treatment. Thus, we conducted this survey among infertile patients in a reproductive medicine center, between September 2021 and December 2021, to estimate the prevalence of COVID-19 vaccine hesitancy and its influencing factors. Information was collected through face-to-face interviews among volunteers. Among the 987 included interviewees, 17.33% reported hesitancy in primary vaccination, 25.63% reported hesitancy in booster vaccination, and 32.32% delayed the primary vaccination. Hesitancy in primary vaccination was associated with unexplained infertility (OR: 1.77, 95% CI: 1.05-2.98), ongoing IVF treatment (OR: 2.17, 95% CI: 1.22-3.89), concerns for vaccine safety (OR: 4.13, 95% CI: 2.66-6.42), effectiveness (OR: 1.62, 95% CI: 1.15-2.28), and influence on pregnancy (OR: 2.80, 95% CI: 1.68-4.67). These factors were also associated with hesitancy in booster vaccination. Delay of the primary vaccination was inversely associated with a college or above degree (OR: 0.49, 95% CI: 0.27-0.87), previous history of influenza vaccination (OR: 0.67, 95% CI: 0.46-0.98), and was positively associated with concerns for the influence on pregnancy (OR: 7.78, 95% CI: 5.01-12.07). It is necessary to carry out targeted education program by health professionals to publicize the benefits of periconception vaccination, and to reduce the resistance to COVID-19 vaccine among infertile couples.

Background Anti-Müllerian hormone (AMH) is used as a biomarker to estimate ovarian reserve. The relationship between AMH and early miscarriage of in vitro fertilization (IVF) is still inconclusive. This study aimed to explore whether serum AMH levels are associated with early miscarriage rates after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) with fresh embryo transfer (ET). Methods This retrospective cohort study included 2246 patients undergoing their first oocyte retrievals for IVF/ICSI with fresh embryos transferred to Tianjin Central Hospital of Gynecology Obstetrics between May 2018 and March 2020. The serum AMH levels of the patients were measured within 12 months before the IVF/ICSI cycles. All women were divided into a low-AMH group, medium-AMH group and high-AMH group. Binary logistic regression was applied to confirm whether the serum AMH level was associated with the risk of early miscarriage independent of potential confounders, such as age, body mass index (BMI), duration of infertility, main diagnosis, history of internal medicine diseases, number of oocytes retrieved and high-quality embryo rate. Results The early miscarriage rate was significantly lower in the medium-AMH group than in either the low-AMH or high-AMH group among young (P = 0.015). In women above 35 years of age, the early miscarriage rates in the three AMH groups were not significantly different. Young women with high serum AMH levels had a significantly higher risk of early miscarriage regardless of age or other potential confounders (adjusted odds ratio (OR) 2.382, 95% confidence interval (CI) 1.246 to 4.553, P = 0.009). The results remained similar after restricting the analysis to women without polycystic ovary syndrome (PCOS). Conclusions With a high AMH level, young women had a higher risk of early miscarriage than women with a medium AMH level in their first IVF/ICSI treatment. In young women, serum AMH levels were independently associated with the risk of early miscarriage after IVF-ET treatment. Serum AMH levels might be a valuable marker to estimate the risk of early miscarriage. It is worth noting to the clinical value of AMH.

Background Type 3 fibroids are a special subtype of intramural fibroids that are likely to affect the pregnancy outcomes of assisted reproductive techniques. Hysteroscopic resection is a treatment for type 3 fibroids, but there has few study of its efficacy to date. In this study we evaluated the effect of hysteroscopic resection of type 3 fibroids on the pregnancy outcomes in infertile women. Methods This retrospective case–control study was conducted from January 1, 2014 to June 30, 2021. Patients who underwent IVF-ICSI in our unit were divided into a type 3 fibroid group and a hysteroscopic myomectomy group. The inclusion criteria for the type 3 fibroid group and the hysteroscopic myomectomy group were as follows: 1) age ≤ 40 years; 2) fibroid diameter or total fibroid diameter > 2.0 cm. The following exclusion criteria were used: 1) oocyte donor treatment cycles and 2) presence of chromosomal abnormalities; 3) history of other uterine surgery; 4) presence of intracavitary lesions, including submucosal fibroids; 5) single fibroid > 5.0 cm; 6) cervical fibroids; 7) unclear ultrasound description of fibroids; 8) preimplantation genetic testing was performed and 9) congenital or acquired uterine malformations. The control group in our study was selected from patients who were treated with IVF only because of fallopian tube factors. According to the age of the type 3 fibroid group and hysteroscopic myomectomy group, random sampling was carried out in the patients between 25 and 47 years of age to determine a control group. The outcomes measured included the average transfer times to live birth, cumulative clinical pregnancy rate, and cumulative live birth rate. Results A total of 302 cycles were enrolled in our study, including 125 cycles with type 3 fibroids, 122 cycles with hysteroscopic myomectomy, and 139 cycles of control patients. The average transfer times to live birth were significantly higher in the type 3 fibroid group than in the other two groups. The frequency of cumulative live births in the type 3 fibroid group was significantly lower than that in the control group. Compared with the control group, the hysteroscopic myomectomy patients had no statistically significant differences in the cumulative clinical pregnancy rate and cumulative live birth rate. Conclusions Type 3 fibroids significantly reduced the cumulative live birth rate of IVF patients. Ultrasound-guided hysteroscopic myomectomy can be used as a treatment for type 3 fibroids and could improve the pregnancy outcomes in infertile women.

Background Due to various iatrogenic and social factors, the global caesarean delivery (CD) rate has risen sharply in the past 30 years. It is more complicated and dangerous for women with a scarred uterus to experience pregnancy again than for women with a previous vaginal delivery (VD). In this study we investigated the impact of previous caesarean delivery (CD) and caesarean scar defects (CSDs) on pregnancy outcomes after in vitro fertilization frozen-thawed embryo transfer (IVF-FET). Methods We conducted a retrospective cohort study that included 1122 women aged Results In SET patients, the clinical pregnancy and live birth rates were decreased in the CSD group compared with the VD and CD groups. In DET patients, the clinical pregnancy and live birth rates were significantly lower in theCSD group than in the CD and VD groups. After adjustment for confounders, previous CD and CSD were associated with a significantly lower clinical pregnancy rate and live birth rate than previous VD in the total sample. This effect was observed in DET patients, but not in SET patients. Additionally, DET patients with previous CD had a significantly higher multiple pregnancy rate (AOR = 0.47, 95% CI = 0.29, 0.75, P = 0.002) than those with previous VD, but no significant associations were observed in CSD and multiple pregnancies (AOR = 0.55, 95% CI = 0.23, 1.34, P = 0.192) between DET patients with CD and those with VD after adjusting for potential confounders. Conclusions Our study showed that during an FET cycle, previous CD and the presence of a CSD could negatively affect pregnancy outcomes especially in DET patients.

Backgroup Frozen-thawed embryo transfer is rising worldwide. One adverse effect of programmed frozen embryo transfer (FET) reported in some studies is an increased risk of adverse obstetric and perinatal outcomes. Meanwhile, body mass index (BMI) also has adverse effect on obstetric and perinatal outcomes. In this study, we investigated that the influence of different endometrial preparation protocols on obstetric and perinatal outcomes and the role of BMI in it. Method This retrospective cohort study included 2333 singleton deliveries after frozen-thaw embryo transfer at our centre between 2014 and 2021, including 550 cycles with programmed FET, 1783 cycles with true natural cycle FET (tNC-FET). In further analysis according to BMI grouped by Asian criterion, group A (18.5 kg/m2 ≤ BMI 2) included 1257 subjects, group B (24 kg/m2 ≤ BMI 2) included 503 subjects and group C (BMI ≥ 28 kg/m2) included 573 subjects. Baseline characteristics of the two groups were compared and analyzed. Binary logistic regression analyses were performed to explore the association between obstetric and perinatal outcomes and endometrial preparation protocols. Results There were no significant differences in the placenta previa, gestational diabetes mellitus(GDM), preterm premature rupture of membranes (PPROM), cesarean section (CS) and macrosomia between the tNC-FET and programmed FET groups (P > 0.05). The programmed FET cycles were associated to a higher risk of pregnancy-induced hypertension (PIH) compared with the tNC-FET cycles (7.3% vs 4.4%, crude OR 1.71[1.16–2.54]; adjusted OR 1.845[1.03–3.30]). After dividing the patients into three groups according to the BMI, The programmed FET cycles were associated to a higher risk of PIH in group C (14.4% vs 6.2%, crude OR 2.55 [1.42–4.55]; adjusted OR 4.71 [1.77–12.55]) compared with the tNC-FET cycles. But there was no statistically significant difference in group A and group B. Programmed FET group compared with the tNC-FET group, the risk of PIH increase as the body mass index increase. Conclusion This study showed a tendency toward increasing risk of PIH in programmed FET cycle compared with the tNC-FET cycle, and the risk of PIH increases as BMI increases. Increased risk of preterm birth and low birth weight is linked to increased risk of PIH.

Phthalates (PAEs) are widely used plasticizers drawing increasing concern due to reproductive toxicity. However, studies on serum PAEs metabolites (mPAEs) and their associations with human ovarian function remain very scarce. In this study, from April 2019 to August 2020, a total of 297 women of childbearing age were recruited in Tianjin, China. Eleven mPAEs were analyzed in serum samples and eight mPAEs were detected at frequencies65% with median concentrations of 0.43-15.3 ng/mL. In multinomial logistic analysis, an increase in serum mono (2-isobutyl) phthalate (miBP) was associated with decline in antral follicle count (AFC) (OR=1.26, 95% CI: 0.99, 1.61) and 5-mono-(2-ethyl-5-hydroxyhexyl) phthalate (mEHHP) was significantly associated with AFC increase (OR=1.43, 95% CI: 1.06, 1.92), which were aligned with the associations found between mPAEs and AMH through generalized linear regression. In multiple linear regression models, per 10% increase in serum mono (2-ethylhexyl) phthalate (mEHP), mono (2-ethyl-5-oxohexyl) phthalate (mEOHP) (oxo-mEHP), and principal component 1 featured for high concentrations of mono-n-butyl phthalate (mBP), miBP and mEHP were associated with 0.15 (95% CI: -0.29, -0.02), 0.01 (95% CI: -0.01, 0.00) and 0.01 (95% CI: -0.02, 0.00) ln-unit decrease in estradiol (E2) levels, respectively, while mono-[(2-carboxymethyl) hexyl] phthalate (mCMHP) (carboxymethyl-mEHP) was positively associated with 0.05 ln-unit increase of E2 (95% CI: 0.02, 0.08). The observed negative associations between mPAEs and the Anti-Müllerian hormone (AMH) also aligned with the change in AFC. Generalized linear regression also revealed nonlinear associations between mono-ethyl phthalate (mEP), mCMHP and follicle-stimulating hormone (FSH). Overall, serum mEHP and its metabolites were negatively associated with E2. miBP was negatively associated with AFC. The nonlinear associations between mPAEs and FSH, and AMH need further study.

The inflammatory microenvironment has been demonstrated to play a role in folliculogenesis, ovulation and premature ovarian failure (POF), as well as infertility. In this study, we aimed to explore the role of inflammation in modulating growth and apoptosis in granulosa cells (GCs), the main components of ovarian follicles. ELISA was used to analyze the levels of inflammatory factors (IL-1β, IL-4, IL-6 and IL-10) in follicular fluid samples and GCs derived from POF patients and healthy normal individuals. CCK-8, flow cytometry and TUNEL assays were used to assess the effect of IL-4 on GC growth and apoptosis. Western blotting was used to examine the effect of IL-4 on the activation of PI3K/Akt, Erk1/2 and Jnk signaling. The results showed that IL-4, IL-1β and IL-6 levels were increased in follicular fluid samples and GCs derived from POF patients compared with those from healthy individuals. GC growth was weakened when cells were treated with IL-4, while apoptosis was increased. In addition, IL-4 increased the level of p-Akt/Akt in GCs. In addition, LY294002, an inhibitor of PI3K, abolished the effect of IL-4 by inhibiting GC growth and promoting apoptosis. In summary, this study demonstrated that IL-4 levels were increased in POF samples and that IL-4 could inhibit GC growth and induce GC apoptosis by activating PI3K/Akt signaling.

Background Caesarean section rates are rising worldwide. One adverse effect of caesarean section reported in some studies is an increased risk of subfertility. Only a few studies have assessed the relationship between the previous mode of delivery and in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) reproductive outcomes. In this study, we primarily investigated the impact of a history of caesarean section with or without defects on IVF/ICSI-ET outcomes compared to a vaginal delivery history. Methods This retrospective study included 834 women who had a IVF or ICSI treatment at our centre between 2015 and 2019 with a delivery history. In total, 401 women with a previous vaginal delivery (VD) were assigned to the VD group, and 433 women with a history of delivery by caesarean section were included, among whom 359 had a caesarean scar (CS) without a defect and were assigned to the CS group and 74 had a caesarean section defect (CSD) and were assigned to the CSD group. Baseline characteristics of the three groups were compared and analysed. Binary logistic regression analyses were performed to explore the association between clinical outcomes and different delivery modes. Results There were no significant differences in the live birth rate, biochemical pregnancy rate, clinical pregnancy rate, mean implantation rate or abnormal pregnancy rate between the CS and VD groups However, the live birth rate and mean implantation rate in the CSD group were significantly lower than those in the VD group (21.6 vs 36.4%, adjusted OR 0.50 [0.27–0.9]; 0.25 ± 0.39 vs 0.35 ± 0.41, adjusted OR 0.90 [0.81–0.99]). Among women aged ≤ 35 years, the subgroup analyses showed that the live birth rate, biochemical pregnancy rate, clinical pregnancy rate, and mean implantation rate in the CSD group were all significantly lower than those in the VD group (21.4 vs 45.8%, adjusted OR 0.35[0.15 ~ 0.85]; 38.1 vs 59.8%, adjusted OR 0.52[0.24–0.82]; 31.0 vs 55.6%, adjusted OR 0.43[0.19–0.92]; 0.27 ± 0.43 vs 0.43 ± 0.43, adjusted OR 0.85[0.43 ± 0.43]). For women older than 35 years, there was no statistically significant difference in any pregnancy outcome among the three groups. Conclusions This study suggested that the existence of a CS without a defect does not decrease the live birth rate after IVF or ICSI compared with a previous VD. However, the presence of a CSD in women, especially young women (age ≤ 35 years), significantly impaired the chances of subsequent pregnancy.

Global decline in male fertility and their associations with ubiquitous exposure of phthalates (PAEs) have raised public concerns. However, the current epidemiological data are limited and controversial. Hence, we investigated possible associations between PAE exposure and male infertility. Eleven phthalate metabolites (mPAEs) were determined in urine and serum samples collected from eighty-eight males diagnosed with infertility from Tianjin, China. The median serum levels of mPAE were n.d. −3.63 ng/mL, which were 1–2 orders of magnitude lower than the urinary levels of n.d. −192 ng/mL. Negative associations were identified between urinary follicle-stimulating hormone (FSH) and MiBP and serum MCMHP, as well as testosterone (T) and luteinizing hormone (LH) and the molar concentrations of ∑mPAE, while positive association was found between T and the serum molar concentrations of ∑mDEHP. Positive associations were found between the molar concentrations of serum ∑mPAE and sperm concentration, sperm motility rate, and progressive motility, between mono (2-ethyl-5-carboxypentyl) phthalate (MECPP) and semen volume and total sperm number, and between MCMHP and progressive motility, while negative association was found between mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) and progressive motility. Moreover, FSH was found to mediate the association between serum concentrations of MCMHP and progressive motility (mediation ratio = 41.6%), and LH to mediate the associations between serum concentrations of ∑mPAE and sperm concentration (mediation ratio = 45.7%) and sperm motility rate (mediation ratio = 29.0%). These results also suggested that serum levels of mPAE are a good predictor for male infertility. Further efforts need to be made on toxicological studies to systematically elaborate the internal mechanisms.

To establish a novel HLA genotyping method for preimplantation genetic diagnonis (PGD) using multiple displacement amplification-polymerase chain reaction-sequencing based technique (MDA-PCR-SBT).Peripheral blood samples and 76 1PN, 2PN, 3PN discarded embryos from 9 couples were collected. The alleles of HLA-A, B, DR loci were detected from the MDA product with the PCR-SBT method. The HLA genotypes of the parental peripheral blood samples were analyzed with the same protocol. The genotypes of specific HLA region were evaluated for distinguishing the segregation of haplotypes among the family members, and primary HLA matching was performed between the embryos.The 76 embryos were subjected to MDA and 74 (97.4%) were successfully amplified. For the 34 embryos from the single blastomere group, the amplification rate was 94.1%, and for the 40 embryos in the two blastomeres group, the rate was 100%. The dropout rates for DQ allele and DR allele were 1.3% and 0, respectively. The positive rate for MDA in the single blastomere group was 100%, with the dropout rates for DQ allele and DR allele being 1.5% and 0, respectively. The positive rate of MDA for the two blastomere group was 100%, with the dropout rates for both DQ and DR alleles being 0. The recombination rate of fetal HLA was 20.2% (30/148). Due to the improper classification and abnormal fertilized embryos, the proportion of matched embryos HLA was 20.3% (15/74),which was lower than the theoretical value of 25%.PGD with HLA matching can facilitate creation of a HLA-identical donor (saviour child) for umbilical cord blood or bone marrow stem cells for its affected sibling with a genetic disease. Therefore, preimplantation HLA matching may provide a tool for couples desiring to conceive a potential donor progeny for transplantation for its sibling with a life-threatening disorder.

In order to establish a simple and useful way for preimplantation genetic diagnosis (PGD) of chromosomal diseases in general IVF laboratory, the methods that are most commonly used in the embryo biopsy, fixation of blastomere and fluorescence in situ hybridization were compared. The three aspects of PGD were analyzed respectively. There was no significant difference in further development capacity of embryos between mechanical (79.7%) and chemical biopsy group (78.6%) (P0.05). In this study, more cells were successfully fixed with the Tween/HCL method (93.8%) than with the methanol/acetic acid method (80.5%, P0.05). There was no significant difference in cytoplasm remains between methanol/acetic acid method and Tween/HCL method (P0.05). The hybridization efficiency of fluorescence in situ hybridization was 89.5% in successive denaturation method and 90.9% in codenaturation method with the difference being not significant (P0.05). In conclusion, the mechanical or chemical method, Tween/HCL fixation method and codenaturation fluorescence in situ hybridization method can constitute a simple and useful way for PGD of chromosomal diseases.