Live Birth Outcomes for PCOS Patients Under the Follicular-Phase Long-Acting GnRH Agonist Protocol or Antagonist Protocol - A Retrospective Chinese Cohort.

Objective: For patients with polycystic ovary syndrome (PCOS) to undergo in vitro fertilization (IVF) and embryo transfer (ET), there has been no consensus regarding which protocol is the most optimal for live birth rate in fresh cycles. We sought to evaluate depot gonadotropin-releasing hormone (GnRH) agonist protocol versus GnRH antagonist protocol in IVF outcomes for PCOS patients in a single fertility center. Methods: In this retrospective cohort, PCOS patients who visited the Second Hospital of Hebei Medical University reproductive center between February 2012 and December 2019 were screened, and 533 PCOS infertility patients were included undergoing their first IVF cycle, with 470 in the depot GnRH agonist group and 63 in the GnRH antagonist group. The primary of this study outcome was the fresh live birth rate (LBR). Results: PCOS women in the depot GnRH agonist group had a higher LBR (49.79%) than those in the GnRH antagonist group (34.92%, p = 0.027). The multivariable logistic regression also confirmed that women in the depot GnRH agonist group had a higher LBR than those in the GnRH antagonist group (OR = 1.83, 95% CI 1.05~3.18, p = 0.032). After propensity score matching (PSM), the LBR in the depot GnRH agonist group was higher (50.32%) than that of the GnRH antagonist group (35.48%), p = 0.033. The ovarian hyperstimulation syndrome (OHSS) rates were similar between the two groups, with 35 in the depot GnRH group and 6 in the GnRH antagonist group (p = 0.561). Conclusions: For PCOS patients in fresh embryo transfer cycles, the depot GnRH agonist protocol may lead to a higher LBR than the antagonist protocol with satisfied lower OHSS rates.

Impact of Insulin Resistance on Ovarian Sensitivity and Pregnancy Outcomes in Patients with Polycystic Ovary Syndrome Undergoing IVF.

BACKGROUND: Ovarian sensitivity index (OSI) is an accurate index to reflect the ovarian sensitivity to exogenous gonadotropins in in vitro fertilization (IVF). How insulin resistance (IR) affects OSI and pregnancy outcomes during IVF remains unclear. METHODS: This was a large retrospective, cohort study. A total of 2055 women with polycystic ovary syndrome (PCOS) undergoing the first fresh IVF cycle were enrolled. They were grouped into terciles based on the homeostasis model assessment of insulin resistance (HOMA-IR) values as control, medium and IR group for comparison. Multivariate regression analysis was also conducted. RESULTS: HOMA-IR had a significantly negative impact on OSI (adjusted ß = -0.24; 95% CI, -0.35 to -0.13), especially in lean patients with an adjusted ß of -0.33 (95% CI, -0.51 to -0.16). The interaction analysis revealed an interactive association between HOMA-IR and body mass index (BMI) (p = 0.017). IR was related to an increased early miscarriage risk independently with an odds ratio (OR) of 2.21 (95% CI, 1.13 to 4.33), without significant impact on pregnancy and live birth rate. CONCLUSION: IR decreased the ovarian response in PCOS patients undergoing IVF, especially in the lean subgroup. IR may result in a higher risk of early miscarriage, but did not impair pregnancy and live birth rate.

The optimal number of embryo cells for effective pregnancy and decrease of multiple pregnancy rate in frozen-thawed embryo transfer.

To investigate the effect of the number of embryo cells on the clinical outcome of frozen-thawed embryo transfer and explore the optimal policy for decreases of multiple pregnancy rate, patients who experienced day 3 vitrified double frozen-thawed embryo transfer were retrospectively analyzed. According to the number of embryonic cells in each pre-frozen embryo, the patients were divided into six groups: 8C2 (two 8-cell embryos), 8C1- < 8C1 (one 8-cell embryo and one under-8-cell embryo), 8C1- > 8C1 (one 8-cell embryo and one over-8-cell embryo), < 8C2 (two under-8-cell embryos), < 8C1- > 8C1 (one under-8-cell embryo and one over-8-cell embryo), and > 8C2 (two over-8-cell embryos). The clinical data were analyzed. The classification decision tree was used to analyze the optimal transfer strategy. A total of 2184 cycles of day 3 vitrified double frozen-thawed embryo transfer were enrolled. In day 3 double frozen-thawed embryo cycles, the 8C2 group and 8C1- > 8C1 group had significantly (P < 0.05) higher pregnancy and multiple pregnancy rates than the other groups. No significant (P > 0.05) difference existed in the pregnancy rate and live birth rate between the 8C1- < 8C1 group, 8C2 group and 8C1- > 8C1 group, but the implantation rate and multiple pregnancy rate in the 8C1- < 8C1 group were significantly (P < 0.05) lower than in the other two groups. Compared with the multiple pregnancy rate of all cycles, the cycles in two branches showed significantly (P < 0.05) higher multiple pregnancy rates (≤ 29 years old: 8C2 / 8C1- > 8C1; 29 < age ≤ 36 years for the first transfer: 8C2 / 8C1- < 8C1 / 8C1- > 8C1, one branch showed similar rate (≤ 29 years old: 8C2 / 8C1- > 8C1) for the first transfer, and the remaining four branches demonstrated significantly (P < 0.05) lower rates. The clinical pregnancy rates before and after optimization were 51.0% vs 50.5%, and the multiple pregnancy rates were 38.5% vs 16.9%. In conclusion, the number of pre-frozen embryonic cells is an important factor affecting the clinical outcome of frozen-thawed embryo transfer in day 3 double good embryos frozen-thawed cycles. The age of patient, number of embryo cells, and the first time of transfer are the most valuable parameters for prediction. For women ≤ 29 years old, the single embryo transfer (SET) strategy was to choose an embryo ≥ 8 cells, and for women with < 29 age ≤ 36 years old, the SET strategy in the first transfer was to choose an embryo ≥ 8 cells.

Evaluation of serum biomarkers and efficacy of MTX in women with ectopic pregnancy.

Ectopic pregnancy occurs when a fertilized ovum attaches outside the uterus. As a complication in approximately 1­2% of all pregnancies, ectopic pregnancies may cause catastrophic hemorrhage as a result of invading maternal blood vessels. Therefore, early diagnosis and timely treatment are crucial for women with ectopic pregnancy. In this study, we aimed to identify and determine the efficacy of serum biomarkers for the prompt diagnosis of ectopic pregnancy. For this purpose, the serum concentrations of progesterone, ß human chorionic gonadotropin (ß­hCG) and cancer antigen­125 (CA125) were detected by solid­phase, competitive binding chemiluminescent enzyme immunoassays. Flow cytometry was used to analyze the percentage of CD3+ T cells in women with ectopic pregnancy. Pathological analysis of tubal and villus tissues was performed by hematoxylin and eosin (H&E) staining. After receiving an injection of methotrexate (MTX), patients were examined by transvaginal ultrasound to detect the size of the echogenic mass. The results revealed that the serum levels of progesterone, ß­HCG and CA125 were significantly decreased in women with ectopic pregnancy, whereas the percentage of CD3+ T cells was increased in women with ectopic pregnancy. Histopathological examination revealed blood clots with small tissue fragments of a tubal­type epithelium and incomplete pile structures. Five days after the MTX injection, an echogenic mass was found with a size of 1.7x1.2x1.6 cm that contained a gestational sac­like structure and a yolk sac. On the whole, the findings of this study indicate the at the joint detection of progesterone, ß­HCG, CA125 serum levels and the CD3+ T cell percentage could be applied as a reliable indicator for the early diagnosis of ectopic pregnancy. MTX administration was determined to be an efficacious approach for the treatment of ectopic pregnancy.

Effects of controlled ovarian stimulation on thyroid stimulating hormone in infertile women.

OBJECTIVE: To study the effects of long-acting gonadotropin-releasing hormone agonist (GnRH-a) on thyroid function in euthyroid patients of in vitro fertilization (IVF)/ intracytoplasmic sperm injection of embryo transfer (ICSI-ET) and to investigate the timing and alteration of thyroid stimulating hormone (TSH) during controlled ovarian stimulation(COS). MATERIALS AND METHODS: Euthyroid patients scheduled for IVF/ICSI were enrolled. Euthyroidism was defined as having no history of hypothyroidism with normal TSH before IVF. Long GnRH-a protocol was chosen as COS protocol. 207 patients were divided into two groups based on basal serum TSH level: group A with 0.35mIU/L＜TSH＜2.5mIU/L (n = 137) and group B with 2.5mIU/L ≤ TSH＜4.5mIU/L (n = 70). Serum TSH was tested on 6 time points: before COS (2-5days in menstrual cycle, before GnRH-a injection), Gn injection day 1, Gn injection day 5, human chorionic gonadotropin (HCG) day, 14 and 28 days after transplantation. The serum TSH, clinical pregnancy and abortion rate were investigated. RESULT: The serum TSH value was significantly (P < 0.05) increased after injection of long-acting GnRH-a in all patients. Both groups had significant (P < 0.05) increases in serum TSH level after long-acting GnRH-a injection. The TSH level was increased in 131(63.3%) patients after GnRH-a injection, of which twenty (9.7%) had subclinical hypothyroidism with TSH level over 4.5 mIU/L. The other 76 (36.7%) patients had decreased TSH. In group A, 79 (57.7%) patients showed an increase of TSH, including three patients (2.2%) with simultaneous rise of TPOAb and four (2.9%) diagnosed of subclinical hypothyroidism with TSH level over 4.5 mIU/L, and the rest fifty-eight (42.3%) patients had decreased TSH with one patient with elevated TPOAb who was diagnosed with subclinical hyperthyroidism. In group B, fifty-two (74.3%) patients showed an increase of TSH, including thirteen (18.6%) patients with elevated TPOAb and sixteen (22.9%) patients diagnosed of subclinical hypothyroidism with TSH level over 4.5 mIU/L, and the rest eighteen (25.7%) patients had decreased TSH with one patient diagnosed with subclinical hyperthyroidism. Group B had a significant higher proportion of patients with elevated serum TSH than group A (P ＜ 0.05). Compared to the baseline level, serum TSH ascended distinctly and reached peak level on HCG day in all patients. Group A and B had similar trends of alteration. Patients in group A had significantly (P＜0.05) higher clinical pregnancy rate than in group B. No significant (P＞0.05) difference in abortion rate were observed between the two groups. CONCLUSION: GnRH-a can significantly increase serum TSH levels with possible development of subclinical thyroid dysfunction. Infertile patients with serum TSH > 2.5 mIU/L are more susceptible to GnRH-a while patients with basal TSH less than 2.5 mIU/L may get a higher clinical pregnancy rate when receiving IVF/ICSI.

Anandamide reduces intracellular Ca2+ concentration through suppression of Na+/Ca2+ exchanger current in rat cardiac myocytes.

PURPOSE: Anandamide, one of the endocannabinoids, has been reported to exhibit cardioprotective properties, particularly in its ability to limit the damage produced by ischemia reperfusion injury. However, the mechanisms underlying the effect are not well known. This study is to investigate whether anandamide alter Na(+)/Ca(2+) exchanger and the intracellular free Ca(2+) concentration ([Ca(2+)]i). METHODS: Na(+)/Ca(2+) exchanger current (I(NCX)) was recorded and analysed by using whole-cell patch-clamp technique and [Ca(2+)]i was measured by loading myocytes with the fluorescent Ca(2+) indicator Fura-2/AM. RESULTS: We found that I(NCX) was enhanced significantly after perfusion with simulated ischemic external solution; [Ca(2+)]i was also significantly increased by simulated ischemic solution. The reversal potential of I(NCX) was shifted to negative potentials in simulated ischemic external solution. Anandamide (1-100 nM) failed to affect I(NCX) and [Ca(2+)]i in normal solution. However, anandamide (1-100 nM) suppressed the increase in INCX in simulated ischemic external solution concentration-dependently and normalized INCX reversal potential. Furthermore, anandamide (100 nM) significantly attenuated the increase in [Ca(2+)]i in simulated ischemic solution. Blocking CB1 receptors with the specific antagonist AM251 (500 nM) failed to affect the effects of anandamide on I(NCX) and [Ca(2+)]i in simulated ischemic solution. CB2 receptor antagonist AM630 (100 nM) eliminated the effects of anandamide on I(NCX) and [Ca(2+)]i in simulated ischemic solution, and CB2 receptor agonist JWH133 (100 nM) simulated the effects of anandamide that suppressed the increase in I(NCX) and [Ca(2+)]i in simulated ischemic solution. In addition, pretreatment with the Gi/o-specific inhibitor pertussis toxin (PTX, 500 ng/ml) eliminated the effects of anandamide and JWH133 on I(NCX) in simulated ischemic solution. CONCLUSIONS: Collectively, these findings suggest that anandamide suppresses calcium overload through inhibition of I(NCX) during perfusion with simulated ischemic solution; the effects may be mediated by CB2 receptor via PTX-sensitive Gi/o proteins. This mechanism is importantly involved in the anti-ischemia injury caused by endocannabinoids.