Effect of Hyperinsulinemia and Insulin Resistance on Endocrine, Metabolic, and Reproductive Outcomes in Non-PCOS Women Undergoing Assisted Reproduction: A Retrospective Cohort Study

Objective: To evaluate the effect of hyperinsulinemia (HI) and insulin resistance (IR) on endocrine, metabolic, and reproductive outcomes in women without polycystic ovary syndrome (PCOS) undergoing assisted reproduction.Materials and Methods: The study included 1,104 non-PCOS women undergoing in vitro fertilization/intracytoplasmic sperm injection-fresh embryo transfer. HI was evaluated by serum fasting insulin (FIN), and IR was evaluated by homeostatic model assessment of insulin resistance index (HOMA-IR). In addition, biometric, sex hormone, and metabolic parameters were measured. Independent t-test, linear, and logistic regression examined associations between HI, IR, and endocrine, metabolic, ovarian stimulation characteristics, and reproductive outcomes.Results: Women with HI and IR had lower levels of progesterone, luteinizing hormone, follicle-stimulating hormone, estradiol, high-density lipoproteins, and increased levels of triglycerides low-density lipoproteins. For ovarian stimulation characteristics, those with HI and IR had a longer duration of stimulation, a higher total gonadotropin dose, and a lower peak estradiol level. Linear regression confirmed these associations. For reproductive outcomes, HI and IR were not associated with clinical pregnancy, live birth, and miscarriage.Conclusions: HI and IR did not impair reproductive outcomes in non-PCOS women undergoing assisted reproduction.

Early Serum Progesterone Measurement on 9th Day after Oocyte Retrieval can be used as a Predictor of Fresh Intracytoplasmic Sperm Injection Cycle Success

BACKGROUND: In intracytoplasmic sperm injection (ICSI) infertility treatment cycles, measuring serum Progesterone level at day 9 after oocyte retrieval could be used as a predictor of success. METHODS: Sixty-nine women were prospectively included in this study, treated with fresh embryo transfer ICSI cycles. Progesterone analyses were performed on the day of oocyte pick up (day 0) at serum and follicular fluid, then re-assessment at serum on day 9 after oocyte retrieval. The data were compared to evaluate the correlation among hormones measured on day 0 and day 9 with pregnancy rate. RESULTS: Pregnancy rate of Iraqi women was 22% (n = 15), mean serum progesterone on day 9 among pregnant ladies was (mean ± SD, 39.5 ± 13.0) which was significantly higher than that who failed to get pregnant (mean 23.2 ± 11, p = 0.001), then after adjustment of the baseline readings (day 0) estimated mean = 11.1. The differences were still significant, receiver operating characteristic curve area showed that serum Progesterone on day 9 after pick up can differentiate correctly between those who will conceive and those who will not, with a sensitivity = 0.933 and specificity = 0.519, at cut off point = 22.33 and above, (Area under the curve = 0.822, p = 0.001). CONCLUSION: Serum progesterone on day 9 could be one of the predictors of endometrial receptivity and pregnancy, which is actually of great value for both doctors and patients during that stressful period till the date of confirmation, which might negatively affect treatment outcome, as well as the psychosocial and pharmacological impact of medication and limited activity for a failed one.

EMBRYO GLUE AND CLINICAL PREGNANCY RATES IN ICSI EMBRYO TRANSFER CYCLES: A PROSPECTIVE STUDY

Purpose: One of the reasons for failed implantation after transferring good quality embryos in an intracytoplasmic sperm injection cycle is the failure of creation a viscid layer between the embryo and the endometrium. Many modifications have been made in embryo transfer medium to improve implantation and increase pregnancy rates such as adding albumin as a source of energy and adding hyaluronic acid in high concentrations such as in Embryo Glue medium: a human embryo transfer medium. To investigate whether the use of Embryo Glue had any effect on clinical pregnancy rates in intracytoplasmic sperm injection-fresh embryo transfer cycles. Methods: A prospective study included one hundred and twenty-eight infertile Iraqi women who were selected and subjected to a stimulation protocol in an intracytoplasmic sperm injection-fresh embryo transfer cycle. All patients were considered to be eligible for embryo transfer (no visible causes could prevent implantation) and only good quality embryos were transferred to them. Those women were divided randomly into two groups according to type of embryo transfer medium: group A: Embryo Glue medium. group B: Conventional medium. Then group A was subdivided according to age into: AI (34 women with age < 35 years and represented 50.7%) AII (33 women with age ≥ 35 years and represented 49.3%) While group B was subdivided into: BI (41women with age < 35 years and represented 67.3%) BII (20 women with age ≥ 35 years and represented 32.7%). Results: Although there was no significant difference between all groups in causes of infertility, the pregnancy rate was significantly higher in subgroup AII (18 pregnant from 33 women) while only 5 patients became pregnant from 20 patients in subgroup BII. In all women no more than four good quality embryos were transferred, and when total number of transferred embryos was significantly more in group B than group A (P=0.013), the significant increase in pregnancy rates was only observed in subgroup AII (P=0.048). Even though a highly significant difference in number of repeated implantation failure was in group A than group B (P=0.027), the pregnancy rates were significantly higher in group A (P=0.038). Conclusion: This study concluded that using Embryo Glue has a beneficial effect on old women and increase pregnancy rates, also it has a positive effect on pregnancy rates in repeated implantation failure and increases pregnancy rates even if the women is old.

IVF/ICSI outcomes of euthyroid infertile women with TAI: does treating with aspirin plus prednisone matter?

Background Thyroid autoimmunity (TAI) has been associated with adverse pregnancy outcomes. To settle with fertility problem, prescribing aspirin combined with prednisone (P+A) to women positive for antithyroid antibodies (ATA) is frequent in clinical practice, but the real effect remains controversial. Methods A multicenter, retrospective study was conducted in three reproductive centers from 2017 to 2020. We recruited 494 euthyroid infertile women positive for anti-thyroperoxidase and/or thyroglobulin antibodies (TPOAb and TgAb, respectively) with thyroid stimulating hormone (TSH) levels ranging 0.35-4.0mIU/L who were undergoing their first in vitro fertilization and embryo transfer (IVF-ET) cycle. Ultimately, 346 women were included of which 150 women were treated with prednisone (10mg/d) and aspirin (100mg/d), while the remaining 196 women were untreated (control group). Treatment started on the day of embryo transfer and continued until clinical pregnancy was determined. Results Clinical pregnancy rate (CPR) was 57.5% vs. 63.5% in the control and treated groups (P=0.414) for first fresh embryo transfer cycles and 57.8% vs. 61.8% for frozen-thawed embryo transfer cycles (P=0.606). Additionally, the live birth rate (LBR) at the fresh embryo transfer was 49.6% vs. 47.3% in the control and treated groups (P=0.762). Logistic regression revealed that P+A did not improve CPR or miscarriage rates (MR). Furthermore, we observed that low free triiodothyronine (FT3) was associated with high MR. Conclusions Utilizing an adjuvant treatment of P+A after the embryo transfer may be unnecessary in euthyroid women with TAI undergoing their first IVF-ET, regardless of embryo type (fresh or frozen).

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.

The altered immunological status of children conceived by assisted reproductive technology

Background With the increased use of assisted reproductive technology (ART), assessing the potential health risks of children conceived on ART important to public health. Most research in this area has focused on the effects of ART on perinatal, metabolic, and oncological risks in children. Although an increased risk of immune-related diseases has been reported in children born after ART, there are no studies on the immunological status of these children. This study aimed to evaluate the impact of different embryo transfer methods and fertilization strategies on the immune status of the offspring. Methods A total of 69 children born to women treated with ART and a matched control group of 17 naturally conceived (NC) children, all aged from 3 to 6 years, were recruited in the reproductive hospital affiliated to Shandong University. The frequency of immune cells in the peripheral blood was assayed using flow cytometry; plasma cytokine levels were determined by multiplex cytokine immunoassay with human cytokine magnetic beads. Results Compared to children born after natural conception, children born after ART had elevated interferon-γ (IFN-γ) levels, regardless of embryo transfer and fertilization strategies. Children in the fresh-embryo transfer group had significantly higher IL-4 levels and a lower ratio of IFN-γ to IL-4 than those in the NC group ((P = 0.004, 10.41 ± 5.76 pg/mL vs 18.40 ± 7.01 pg/mL, P = 0.023, 1.00 ± 0.48 vs 0.67 ± 0.32, respectively). Similar results were shown in either the in vitro fertilization (IVF) group or the intra-cytoplasmic sperm injection (ICSI) group (P < 0.05 and P = 0.08 for IVF; P < 0.05 and P < 0.05 for ICSI, respectively). These alterations in IL-4 concentrations and the ratio of IFN-γ to IL-4 were statistically significantly correlated with supra-physical E2 (estradiol) levels on the day of hCG administration (R = 0.502, P = 0.017; R = − 0.537, P = 0.010, respectively). Consistently, the frozen embryo transfer did not result in alterations of these immune indicators in the offspring. Overall, there were no significant differences between the ART group and NC group in the frequencies of T cells, B cells, natural killer (NK) cells, CD4+T cells, CD8+T cells, T helper (TH)1 cells, TH17 cells, and regulatory T (Treg) cells and cytokine levels of IL-10 and IL-17a (all P > 0.05). Conclusions Immunological alterations existed in children born after the use of ART. The elevated E2 levels before embryo implantation contributed to the increased IL-4 levels in children conceived by fresh embryo transfer. The assessment of immunological alteration is of importance to children conceived by ART for early monitoring and intervention.

Stress, anxiety, and depression in infertile couples are not associated with a first IVF or ICSI treatment outcome

Background Psychological distress may exert a negative influence on reproductive function of couples at reproductive age. Couples seeking assisted reproductive technology (ART) treatment may have a higher prevalence of psychological distress than fertile couples. However, whether psychological distress is associated with the outcome of ART treatment remains unknown. We aimed to investigate the association of pre-treatment psychological distress and clinical pregnancy rate among infertility couples undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment. Methods This nested case-control study was conducted based on women who underwent their first fresh IVF or ICSI cycle in the Jiangsu Birth Cohort Study (JBC) between November 2015 and January 2019. A total of 150 women who did not obtain clinical pregnancy after first IVF or ICSI fresh embryo transfer were identified as cases, and a total of 300 age matched women who obtained clinical pregnancy were identified as controls. Conditional logistic regression analyses were used to investigate the association between psychological distress and the outcome of first IVF or ICSI treatment, adjusting for multiple potential confounders. Results No statistically significant association was observed between score of maternal symptoms of psychological distress and clinical pregnancy. Adjusted ORs of logistic regression were 1.00 (95% CI 0.97-1.03) for anxiety, 0.98 (95% CI 0.95-1.02) for depression, and 0.98 (95% CI 0.95-1.01) for perceived stress, respectively. When treat depression and anxiety as categorical variables, 62 (13.8%) were classified as clinical depression, 11 (2.4%) were classified as clinical anxiety, among 450 women in the present study. Psychological distress symptoms were also not associated with clinical pregnancy rate. Adjusted ORs of logistic regression were 0.27 (95% CI 0.03-2.33) for anxiety, 0.88 (95% CI 0.46-1.68) for depression, respectively. Conclusions Our findings firstly indicated that psychological distress experienced prior to IVF/ICSI treatment was not associated with clinical pregnancy.

Association between baseline LH/FSH and live-birth rate after fresh-embryo transfer in polycystic ovary syndrome women

This study aimed to retrospectively analyse the effect of the baseline luteinising hormone/follicle-stimulating hormone ratio (bLH/FSH) on the live-birth rate per fresh-embryo transfer cycle (LBR/ET) in infertile women with polycystic ovary syndrome (PCOS) who received a fresh-embryo transfer. A total of 424 patients with PCOS who underwent the first cycle of in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) fresh-embryo transfer at our hospital was enrolled. Univariate and multivariate logistic regression analyses, along with curve fitting and a threshold effect analysis, were performed. Baseline LH/FSH levels were a significant (P < 0.05) independent risk factor affecting live birth. In the first IVF/ICSI antagonist treatment cycles, LBR/ET after fresh-embryo transfer was relatively flat, until bLH/FSH was 1.0; thereafter, it started to decrease by 17% for every 0.1-unit bLH/FSH increase. Considering the decline in LBR/ET, it is recommended that PCOS women with bLH/FSH > 1.0 carefully consider fresh-embryo transfer during their first IVF/ICSI.