Men's Sleep Quality and Assisted Reproductive Technology Outcomes in Couples Referred to a Fertility Clinic: A Chinese Cohort Study.

Background: Poor sleep quality has been linked to lower semen quality, but it is unclear whether this result in decreased fertility. To address this question, we retrospectively evaluated the relationship between men's sleep quality and treatment outcomes in subfertile couples receiving assisted reproductive technology (ART). Patient Enrollment and Methods: From September 2017 to November 2019, 282 subfertile couples referred to a Chinese fertility clinic and eligible for ART procedures were enrolled in our study. Sociodemographic characteristics, life habits, and sleep habits in the year prior to ART were recorded. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). We first divided the patients into two groups based on sleep quality (good sleep: PSQI < 5 and poor sleep: PSQI ≥ 5). Then, the ART outcomes (fertilization rate, good quality embryo rate, implantation rate, positive pregnancy rate, clinical pregnancy rate, live birth rate, miscarriage rate, and birth weight) of each group were analyzed. Finally, multivariate linear and logistic regression analysis were used to examine the relationship between sleep quality (discrete variable or dichotomous variable) and ART outcomes. Results: The participants in the poor sleep group showed a lower fertilization rate of 60.13% (543/903) when compared with 67.36% for the good sleep group (902/1339), P < 0.001. The global PSQI score had a significant influence on birth weight (ß, -63.81; 95% CI, -119.91- -8.52; P = 0.047), and live birth rate (OR, 0.88; 95% CI, 0.78- 0.99; P = 0.047) after adjusting for the interfering factors. Men's sleep quality was unrelated to good quality embryos rate, implantation rate, positive pregnancy rate, clinical pregnancy rate, or miscarriage rate. Conclusion: Men's sleep quality was positively associated with fertilization rate, birth weight, and live birth rate among couples undergoing ART.

Value of serum and follicular fluid sirtuin (SIRT)1 and SIRT2 protein levels in predicting the outcome of assisted reproduction.

BACKGROUND: To explore whether serum and follicular fluid (FF), sirtuin 1 (SIRT1), and SIRT2 could predict the outcome of assisted reproduction. METHODS: All patients underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) for the first time in the Reproductive Medicine Center of the First Affiliated Hospital of Zhejiang University Medical College from March 2018 to December 2018. According to cumulative clinical pregnancy outcomes, the patients were divided into a pregnancy group and non-pregnancy group. We measured the serum levels of SIRT1, SIRT2, anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) from the second to the fifth day of menstruation, and the levels of SIRT1 and SIRT2 in serum and FF on the day of human chorionic gonadotropin (HCG) injection and oocyte retrieval. RESULTS: A total of 125 patients met the inclusion criteria. The pregnancy group comprised 56 cases and non-pregnancy group 69 cases. There were significant differences in basal level SIRT2 (bSIRT2), AMH, antral follicle count (AFC), number of oocytes obtained, number of mature eggs, number of fertilized eggs, number of excellent embryos, number of blastocyst formations, and number of transferred high-quality embryos between the two groups. The area under the curve (AUC) values of bSIRT2, AFC, AMH, and age were significantly different from those under the opportunity reference line (P<0.05). In the subsequent correlation analysis, FFSIRT2, and HCG day serum SIRT2 were negatively correlated with age (r=-0.35, r=-0.19), and positively correlated with AFC (r=0.2, r=0.02). Serum SIRT1 on HCG day was negatively correlated with the number of blastocysts and the number of frozen embryos (r=-0.18, r=-0.21). Levels of FF SIRT1 and FF SIRT2 were significantly lower than those in serum SIRT1 and SIRT2, and there was no significant difference in serum SIRT1 and SIRT2 before and after ovulation promotion. CONCLUSIONS: The results suggest that bSIRT2 has significant statistical significance in predicting the cumulative number of pregnancies. When combined with AMH, AFC, and age, bSIRT2 can predict the cumulative pregnancy outcome. In addition, the level of serum SIRT1 and SIRT2 were not affected by ovulation promotion.

Comparative study of assisted reproductive outcomes between young patients with occult premature ovarian insufficiency and advanced-age patients.

OBJECTIVE: The purpose of this study was to compare the pregnancy outcomes among young patients with occult premature ovarian insufficiency (OPOI), advanced-age patients with diminished ovarian reserve (DOR), and advanced-age patients with normal ovarian reserve. METHODS: We retrospectively reviewed 324 women who underwent their first cycles of in vitro fertilization/intracytoplasmic sperm injection. The women were divided into the following groups: young women with OPOI, advanced-age women with DOR, and advanced-age women with normal ovarian reserve. The outcomes were compared among the different groups. RESULTS: The rates of live birth and embryo implantation in the young OPOI group were significantly higher than in the advanced-age DOR group, but comparable to those in the advanced-age normal ovarian reserve group. Moreover, the abortion rate was significantly lower in young OPOI patients compared with advanced-age patients with or without DOR. CONCLUSION: Higher embryo implantation and live birth rates and a lower abortion rate can be achieved in young patients with OPOI compared with older patients. The better outcomes in advanced-age patients with normal ovarian reserve compared with DOR may be related to egg quantity rather than quality.

Association Between Sleep Quality and Semen Parameters and Reproductive Hormones: A Cross-Sectional Study in Zhejiang, China.

BACKGROUND: The effects of sleep duration on semen quality have been documented in many epidemiological studies. However, the association between sleep quality and semen parameters and reproductive hormones is still unclear. PATIENTS ENROLLMENT AND METHODS: We conducted a cross-sectional study among 970 outpatients from the Reproductive Medicine Center in Zhejiang, China between October 2017 and July 2019. All participants delivered a semen sample, underwent a physical examination, and answered a questionnaire to provide the following information: demographics, life habits, and sleep habits. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). We first divided the patients into two groups according to sleep quality (good sleep: PQSI < 5 and poor sleep: PSQI ≥ 5). Then, we analyzed routine sperm parameters (semen volume, sperm total motility, progressive motility, sperm concentration, total sperm number, and normal sperm morphology) and reproductive hormones (follicle-stimulating hormone, luteinizing hormone, estrogen, testosterone, and prolactin) of each group. Finally, we used multivariate linear regression analysis and Spearman correlation coefficients to examine the relationship between sleep quality (discrete variable or dichotomous variable) and sperm parameters, reproductive hormones. RESULTS: A negative correlation was found between the general PSQI scores and several semen parameters: total motility (r= -0.187979, p< 0.001), progressive motility (r= -0.192902, p< 0.001), concentration (r= -0.167063, p< 0.001), total sperm number (r= -0.160008, p< 0.001), and normal sperm morphology (r= -0.124511, p< 0.001). However, there was no significant correlation between the semen volume, all reproductive hormones and the general PSQI scores. After adjusting for confounders, men with poor sleep had lower total motility (ß= -9.287; 95% CI, -12.050, -6.523), progressive motility (ß= -8.853; 95% CI, -11.526, -6.180), concentration (log scale, ß= -0.131; 95% CI, -0.181, -0.082), total sperm number (log scale, ß= -0.137; 95% CI, -0.189, -0.084), and normal sperm morphology (ß= -1.195; 95% CI, -1.844, -0.547), but semen volume and all reproductive hormones were not markedly altered. CONCLUSION: Poor sleep quality might be related to impaired semen quality, but we found no evidence that poor sleep quality affects reproductive hormones.

The predictive value of anti-Mullerian hormone on embryo quality, blastocyst development, and pregnancy rate following in vitro fertilization-embryo transfer (IVF-ET).

PURPOSE: The objective of this study was to investigate the predictive value of anti-Mullerian hormone (AMH) on fertilization rate (FR), blastocyst development, embryo quality, the outcome of the pregnancy and the live birth rate (LBR) following in vitro fertilization-embryo transfer (IVF-ET)/intracytoplasmic sperm injection (ICSI). METHOD: In this prospective study outcomes were followed in 83 women undergoing cycles of IVF/ICSI within a university hospital. Basal serum AMH, follicle stimulating hormone (FSH), luteinizing hormone (LH) and antral follicle count (AFC) were measured on Day 3. Serum AMH (Gn6 AMH ) level was measured on Day 6 after the administration of gonadotrophin (Gn). AMH was measured in follicle fluid (FF AMH) on the day of ovum pick-up (dOPU). The numbers of retrieved and fertilized oocytes, good quality embryos and blastocysts were counted. Secondary outcome variables included clinical pregnancy rate (CPR) and LBR. RESULTS: Spearman correlation analysis indicated that the numbers of oocytes, good quality embryos and blastocysts were associated with AMH (P < 0.05) and that LBR was correlated with FF AMH (r = 0.495, P < 0.05). No associations were found between FR and AMH (P > 0.05). Receiver operating characteristic analysis showed that the sensitivity of FF AMH at predicting CPR was 91.2%; the specificity was 86.5% and ROC(AUC) was 0.893 (P < 0.0001). CONCLUSION: AMH parameters were correlated with good quality embryos and blastocysts, but only FF AMH showed a significant correlation with LBR and CPR.

[Outcome of pregnancy in women with polycystic ovary syndrome treated by in vitro maturation of immature oocytes].

OBJECTIVE: To investigate pregnancy outcome of infertility women with polycystic ovary syndrome (PCOS) treated by in vitro maturation (IVM) of immature oocytes. METHODS: From Nov. 2003 to Oct. 2007, medical documents of 118 women with PCOS underwent 140 IVM treatment cycles in Reproductive Medical Center of First Affiliated Hospital of Wenzhou Medical College were collected. Follow up of 62 pregnancies were performed by prenatal examination in hospital or telephone query to record perinatal monitoring and pregnancy outcome. RESULTS: There are 62 pregnant women including 5 biochemical pregnancies and 57 clinical pregnancies obtained in 140 transferred cycles, resulting in the pregnancy rate of 40.7% (57/140). The rates of singleton pregnancies, twin pregnancies and triplet pregnancies were 61.4% (35/57), 29.8% (17/57) and 5.3% (3/57), respectively. The rate of ectopic pregnancy was 3.5% (2/57). Seven (7/57, 12.3%) women underwent early abortion during 7 -14 weeks of pregnancy, and 1 case (1/57, 1.75%) with premature rupture of membranes occurred at 22 gestational week. One woman with twin pregnancy spontaneously reduced to singleton at 8 gestational weeks. Totally, the rate of pregnancy complications was 26.3% (15/57) including premature rupture of membranes (1 case), placenta previa (1 case), hypertensive disorder (1 case), preterm delivery (10 cases) and gestational diabetes mellitus (2 cases). Until now 47 women gave birth to 65 infants including 29 singleton infants and 18 twins. One female preterm neonate died after 6 days' delivery due to pneumonia, no malformation was observed on the other neonates. 21.3% (10/47) of deliveries were premature,76.6% (36/47) of deliveries were full-term, 2.1% (1/47) of deliveries were postterm. The mean birth weight was 2972 gram. The rate of infants with low weight was 26.2% (17/65). CONCLUSIONS: A relatively high clinical pregnancy rate has been achieved, the rates of early abortion, ectopic pregnancy, pregnancy complications, perinatal mortality, and neonatal malformation occurring after the treatment of IVM in women with PCOS are not mounting. However, the relative high rates of multiple pregnancies, low birth weight and preterm labor were increased.

[Correlation between serum inhibin B level after treatment with gonadotropin releasing hormone agonist and outcome of in vitro fertilization-embryo transfer].

OBJECTIVE: To evaluate the decreased level of serum inhibin B (INHB) treated by gonadotropin releasing hormone agonist (GNRH-a) in predicting ovarian response and pregnancy in in vitro fertilization-embryo transfer (IVF-ET). METHODS: The prospective study enrolled 124 women given by GnRH-a+ recombine follicle stimulating hormone (rFSH) + human chorionic gonadotrophin (hCG) long term stimulation protocol undergone their first cycle of IVF-ET treatment. The following predictive factors were collected and analyzed, such as age, basal level of follicle stimulating hormone (FSH), the ratio of FSH/ luteinizing hormone (LH), the concentration of INHB after down-regulation, total number of antral follicle count (AFC) and mean ovarian volume. Ovarian response was evaluated by the number of oocytes obtained. A multiple regression analysis and logistic regression model were used for all possible prognostic variables to evaluate the value of different hormones in predicting ovarian response and pregnancy after IVF-ET. Receiver operating characteristic (ROC) analysis was used to evaluate the level of INHB in predicting the number of oocytes obtained. The sensitivity and specificity were calculated at the discriminating cut-off point. RESULTS: The concentration of INHB after down-regulation showed a highly significant positive correlations with the number of oocytes obtained (r = 0.435, P < 0.01). The multiple regression analyses showed INHB was the most significant predictor of the number of retrieved oocytes, but INHB was not associated with IVF-ET outcome significantly (P > 0.05). ROC analyses showed INHB after down-regulation had the largest area under curve (AUC) 0.933 (95%CI: 0.878 - 0.988). When a threshold of 15 ng/L of INHB was established, 95.5% sensitivity and 50.0% specificity in ovarian response were observed. CONCLUSIONS: The level of INHB was the best factor in predicting ovarian response in IVF-ET. Decreased level of INHB was the early sign of ovarian reserve function failure, however, useless in predicting IVF-ET outcome.

[Effect of desogestrel and ethinyl estradiol pretreatment in superovulation cycles with short protocol].

OBJECTIVE: To study the effect of desogestrel and ethinyl estradiol (DEE) pre-treatment combined with gonadotropin releasing hormone agonist (GnRH-a) stimulation in in vitro fertilization-embryo transplantation (IVF-ET). METHODS: A retrospective analysis was performed in 101 infertile women who received a short protocol of GnRH-a for IVF-ET treatment from June 2004 to June 2007 in the Reproductive Medicine Center of First Affiliated Hospital of Wenzhou Medical College. Patients had been pre-treated with oral contraceptive pill (OCP) for two months before GnRH-a combined with recombinant follicle stimulation hormone (r-FSH) treatment (study group, n = 42) or had not been pretreated with OCP (control group, n = 59). A statistical analysis of two groups was carried out for the assessment of ovulation stimulating effect of OCP and its influence on the IVF. RESULTS: Serum FSH was significantly decreased after OCP in the study group. Twelve pregnancies were obtained including 1 case of spontaneous abortion at 7 weeks in the study group, and 11 pregnancies were obtained including 2 cases of spontaneous abortion during 7 -9 weeks in control group. The clinical pregnancy rates in the study group (23%, 12/53) was higher than that in the control group (17%, 11/63), but the differences were not significant (P > 0.05). The miscarriage rate in the study group (8%, 1/12) was lower than that in the control group (18%, 2/11), however no significant differences were found between them (P > 0.05). The cycle cancellation rate in patients of the study group (5%, 3/56)was significantly lower than that in patients of the control group (17%, 13/76, P < 0.05). The differences between patients of the two groups with respect to age, basal level of FSH and luteinizing hormone (LH), antral follicle counts, the mean number of oocyte retrieval, the days of stimulation, total dose of r-FSH used, fertilization rate and embryo cleavage rate, however were insignificant. CONCLUSION: OCP pretreatment combined with short protocol of GnRH-a stimulation in IVF could significantly decrease the cycle cancellation rate, with a declining miscarriage rate and increasing pregnancy rate.

[Analysis of pregnancy outcomes after in vitro fertilization-embryo transfer and intracytoplasmic sperm injection].

OBJECTIVE: To compare pregnancy and perinatal outcomes between in vitro fertilization-embryo transfer (IVF-ET) and intracytoplasmic sperm injection (ICSI). METHODS: A retrospective study was carried out to measure pre-clinical and clinical abortion, ectopic pregnancies, multiple gestations, birth weight, gestational age, congenital malformation and perinatal mortality in patients receiving either IVF-ET (n = 143, group 1) or ICSI (n = 173, group 2) from January 1999 to June 2001. The outcomes of singleton and twin were compared separately. RESULTS: The maternal age, infertility duration, parity and the number of transferred embryo were comparable between the two groups. There were no significant differences in abortion rate (16.1% vs 13.3%), birth rate (65.7% vs 74.6%) between IVF-ET and ICSI groups (P > 0.05). In singleton, the rates of low birth weight, small for gestational age and pre-term birth were 1.8%, 7.3%, 5.5% respectively in IVF-ET group and 6.8%, 8.1%, 14.9% respectively in ICSI group. In twin, the rates of low birth weight, small for gestational age and pre-term birth were 34.2%, 30.3%, 42.1% respectively in IVF-ET group and 42.6%, 38.0%, 46.3% respectively in ICSI group. There were no significant differences between the two groups (P > 0.05). But the rates of low birth weight, small for gestational age and pre-term birth were higher in twin than in singleton (P < 0.01). The incidence of congenital malformation was 2.2% and 1.6% in IVF-ET and ICSI group respectively (P > 0.05). CONCLUSIONS: The pregnancy and perinatal outcomes are similar between IVF-ET and ICSI groups. Twin is the main cause of low birth weight, small for gestational age and pre-term birth.

[Effects of metformin on gonadotropin-induced ovulation in patients with polycystic ovary syndrome].

OBJECTIVE: To evaluate the effects of metformin on gonadotropin-induced ovulation in patients with polycystic ovary syndrome (PCOS). METHODS: Forty patients with PCOS (study group) and 20 women with normal weight and menstrual cycle (control group) were enrolled. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), fasting glucose (FG), fasting insulin (FINS) and fasting leptin were measured before and after treatment. In the study group, 20 cases (group A) were assigned to take 500 mg of metformin three times daily for 12 weeks, if pregnancy did not occur, high purified FSH (FSH-HP) was added for one cycle; another 20 cases (group B) were induced ovulation with FSH-HP alone for one cycle. RESULTS: There were significant high FINS and leptin levels in the study group as compared with the control group [(20 +/- 16) vs (12 +/- 6) nmol/L, P < 0.05; (14 +/- 16) vs (8 +/- 4) mg/L, P < 0.05]. The obese PCOS group had markedly higher serum FINS and leptin than the non-obese PCOS group [(24 +/- 18) vs (14 +/- 8) nmol/L, P < 0.05; (20 +/- 22) vs (8 +/- 4) mg/L, P < 0.05], but serum FINS and FG were not significantly different between the non-obese PCOS and the control group (P > 0.05). After administration of metformin for 12 weeks, serum LH, T, leptin and FINS decreased significantly (P < 0.05 - 0.01), serum FSH levels and body mass index showed a slight decrease, whereas no change was found in FG. In the study group, 3 cases conceived during metformin therapy, the remaining 37 were induced ovulation with FSH-HP or FSH-HP and metformin, 7 cases obtained pregnancy. The rates of ovulation and pregnancy in group A were higher than those in group B (88% vs 70%, 24% vs 15%), but no significant difference was found. CONCLUSIONS: Metformin therapy in PCOS can decrease the FINS and leptin levels, normalize the endocrine abnormalities, resumes ovulation and pregnancy in some patients, and may improve the ovarian response to gonadotropin.

[Endocrine and metabolic effects of metformin in combination with compound cyproterone acetate in women with polycystic ovarian syndrome].

OBJECTIVE: To study the endocrinologic and metabolic effects of metformin in combination with compound cyproterone acetate (CPA) on patients with polycystic ovarian syndrome (PCOS). METHODS: A prospective study involved total 45 PCOS patients as group A and 20 non-PCOS infertility patients as control (group B). Complete baseline work-up including body mass index (BMI), waist/hip ratio (WHR), ferriman-Gallwey score (FGS), gonadotrophin, testosterone (T), sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (Ds), insulin (FI) and glucose tolerance test, were performed in all patients. Patients in group A were treated with CPA alone (group A1), metformin alone (group A2) or combination of CPA with metformin (group A3), respectively by randomization. At the end of 12-week therapy, subjects were re-evaluated and above parameters were measured. RESULTS: Women in group A had significant increases in BMI, WHR, FGS, luteinizing hormone (LH), T, FI, insulin resistance, and significantly decrease in high-density lipoprotein (HDL)-C comparing with the control group (P < 0.01). No significant difference among A1, A2 and A3 was found at baseline. LH, T, free testosterone (FT) were significant decreased from (13.9 +/- 5.9) IU/L, (2.1 +/- 0.8) nmol/L and (2.8 +/- 2.3) nmol/L respectively to (5.8 +/- 2.2) IU/L, (1.2 +/- 0.4) nmol/L and (0.8 +/- 0.5) nmol/L respectively and SHBG was significant increased from (99 +/- 42) nmol/L to (187 +/- 64) nmol/L in group A3, when compared with LH, T and FT from (13.8 +/- 7.6) IU/L, (2.2 +/- 1.1) nmol/L and (2.5 +/- 1.9) nmol/L respectively to (11.8 +/- 6.5) IU/L, (1.8 +/- 0.8) nmol/L and (1.7 +/- 1.0) nmol/L respectively and SHBG from (99 +/- 40) nmol/L to (120 +/- 51) nmol/L in group A2 (P < 0.05 approximately 0.001). HDL-C were significantly increased from (1.5 +/- 0.3) mmol/L to (1.8 +/- 0.3) mmol/L in group A3 comparing with HDL-C from (1.5 +/- 0.4) mmol/L to (1.6 +/- 0.4) mmol/L in group A1 (P < 0.001). CONCLUSIONS: The PCOS patients treated with metformin in combination with compound cyproterone acetate may be more effective in inhibiting hyperandrogen and hypersecretion of LH than metformin alone and more obvious in improving lipid profiles than CPA alone.