The effects of different endometrial preparation regimens on pregnancy outcomes in frozen-thawed embryo transfer cycles: a prospective randomized controlled study.

OBJECTIVE: An increasing number of research have emerged to compare the pregnancy outcomes between the natural cycle and the hormone replacement therapy (HRT) cycle in preparing the endometrium for frozen-thawed embryo transfer (FET), but the results are controversial. This prospective randomized controlled study was hence designed to obtain more solid evidence. MATERIALS AND METHODS: In this study, patients with regular menstrual cycle length (21-35 days) who underwent FET between January 2010 to December 2017 were recruited for this study. Upon further filtering with the selection criteria of patients being, a total of 405 patients were recruited and randomized. Finally, analysis was performed on 384 patients: 178 belonged to the natural cycle group whereas the remaining 206 were in the HRT group. The primary outcome was live birth rate, while the secondary outcomes were implantation rate, clinical pregnancy rate, early miscarriage rate, late miscarriage rate, multiple birth rate and low birth weight rate. RESULTS: The live birth rate (37.6% vs 30.1%, p = 0.119) of natural cycle group were higher than those of the hormone replacement therapy group, although the difference was not significant. The secondary outcomes were not found to differ significantly between the two groups. Nonetheless, the endometrium was found to be thicker in the natural cycle group (10.75 mm) than the HRT group (9.00 mm) (p < 0.001). CONCLUSION: No significant differences were observed between the pregnancy outcomes of the natural cycle group and the HRT group which comprised of patients with regular menstrual cycle length.

The relationship of total progressive motile sperm count with the outcome of IUI? An analysis of 5171 cycles.

Background: The role of motile sperm count in intrauterine insemination (IUI) success rate is controversial. This retrospective cohort study performed among unselected infertile couples undergoing IUI was to explore the association between the total progressive motile sperm count (TPMSC) and the live birth rate (LBR) following IUI.Methods: The total cohort of 5363 cycles, 2666 infertile couples between January 2015 and December 2018 and finally 5171 cycles, 2647 couples were included for analysis in Sun Yat-sen memorial hospital of Sun Yat-sen University. The primary outcome was LBR per cycle. And the secondary outcome measure was clinical pregnancy rate (CPR) per cycle.Results: From the receiver operating characteristic (ROC) analysis of female age predicting live birth, female age cutoff was defined as 28 years. With a female age of ≤28 years, the CPRs were 11.5%, 14.9%, 16.1%, and 15.8% in quartile groups of pre-wash TPMSC, respectively. For the LBRs the values were 9.4%, 12.9%, 14.4%, and 11.3%, and there were also no significant differences in quartile groups of pre-wash TPMSC with ≤24 million (M), [24M-50M], [50M-97M], >97M. No statistically significant differences in the CPRs (p = .051) and LBRs (p = .088) were also observed in the quartiles groups of post-wash TPMSC. With a female age of >28 years, the CPR in couples with post-wash TPMSC ≤22.32 M was significantly lower than with post-wash TPMSC >81.0 M (p = .007). There was an obvious trend in which CPRs and LBRs increased with the post-wash TPMSC during the <81 M interval in women >28 years.Conclusions: The optimal female age cutoff for live birth was 28 years in IUI cycles. Pre-wash and post-wash TPMSC were not significantly associated with CPR and LBR per cycle. When female age >28 years, there was a better outcome with post-wash TPMSC >22.32 million.

Rapamycin preserves the primordial follicle pool during cisplatin treatment in vitro and in vivo.

Rapamycin has been proven to effectively inhibit the activation of primordial follicles while cisplatin-induced the loss of primordial follicles due to the over-activation of the primordial follicle stockpile. Whether rapamycin could inhibit the loss of primordial follicles induced by cisplatin is still unknown. The ovaries of neonatal Sprague Dawley rats were cultured in vitro in different doses of rapamycin (0.08, 0.16, and 0.32 µg/ml) and cisplatin (0.1, 0.4, and 0.8 µg/ml). The immature BALB/c mice were administered cisplatin with or without rapamycin by intraperitoneal injection. Ovaries were collected to analyze the histomorphology, the messenger RNA (mRNA) expression of anti-Mullerian hormone (AMH), growth differentiation factor 9 (GDF9), and bone morphogenetic protein 15 (BMP15) and the expression of key proteins of mammalian target of rapamycin (mTOR) pathway. Growing follicle counts of ovaries cultured in vitro in the R0.16 and R0.32 groups were decreased and the ratio of growing to primordial follicles was also decreased in a dose-dependent manner. In the C0.8 group, growing follicles were decreased compared with the other groups while the ratio was substantially increased in the C0.4 and C0.8 group. Co-treatment attenuated primordial follicle loss and reduced the upregulated ratio induced by cisplatin. Ovarian follicle dynamics in vivo was consistent with the in vitro results. Primordial follicles counts were statistically increased and the ratio was reduced in the rapamycin group compared with the control group. Primordial follicle counts were dramatically reduced in the cisplatin group whereas co-treatment with rapamycin slightly recovered its counts. There was no obvious difference in the number of growing follicles between the cisplatin group and other groups. The ratio was significantly increased in cisplatin-treated mice whereas decreased in the co-treatment group. The apoptosis rate of antral follicles in cisplatin-treated mice was higher than the other groups while the apoptosis rate was decreased in the co-treatment group in vivo. Compared with the control and rapamycin group, the mRNA expression of AMH, GDF9, and BMP15 were downregulated in the cisplatin group. The co-treatment group recovered the mRNA expression of BMP15. In addition, the expression of key protein of mTOR pathway rpS6 and its phosphorylated forms were increased in the cisplatin-treated group while co-treatment decreased their expression. Rapamycin attenuated the loss of primordial follicles induced by cisplatin through the inhibitory effect of rapamycin on the mTOR pathway. These results suggest that rapamycin may be an effective drug for the protection of ovarian function during chemotherapy.

Live Births after in vitro Fertilization with Fertility-Sparing Surgery for Borderline Ovarian Tumors: A Case Series and Literature Review.

This is a case series reporting live births following in vitro fertilization (IVF) after fertility-sparing surgery in patients with borderline ovarian tumors (BOTs). Seventeen patients, in whom fertility-sparing surgery for BOTs followed by IVF was performed from July 1, 2011 to September 30, 2017, in our IVF center, were included. Here we retrospectively present their BOT characteristics and clinical outcomes of assisted reproduction technology (ART) and then discuss the literature on management of patients with BOTs after fertility-sparing surgery. The study sample of 17 patients started IVF-assisted reproduction within a median of 24 months after fertility-sparing surgery. Eight patients achieved live births after IVF followed by fresh or frozen-thawed embryo transfer, and one is currently pregnant after the second IVF treatment. Four of these 17 women experienced 6 recurrences of BOTs after IVF and delivery in a median of 29 months of follow-up. The literature reports a pooled estimate of 63.5% for pregnancy and 21.7% for recurrence of BOTs in patients with the same condition. Pregnancy outcomes of IVF in these women are usually better than those of generally infertile women. Moreover, our review of the literature suggests that ART has no negative impact on the prognosis of BOTs.

Iron overload modulates follicular microenvironment via ROS/HIF-1α/FSHR signaling.

Iron is essential for the health of reproductive system, and women with iron overload suffer from ovarian dysfunction and lack effective treatment in fertility preservation. However, the underlying mechanism of the detrimental effects of iron overload on ovarian function remains ambiguous. Here, we confirmed the excess iron in the circumjacent follicle near endometriomas, which negatively impacted the oocyte development in the affected ovaries. Further, by integrating cell line and chronic iron overload mice model, we demonstrated that iron overload can function as a ROS inducer to amplify mitochondria damage, which significantly elevated the release of cytochrome C and ultimately induced the apoptosis of granular cells. Besides, for the first time, our findings revealed that disruption of HIF-1α/FSHR/CYP19A1 signaling was critical for decreased estrogen synthesis of granular cells in response to iron overload, which can lead to apparent oocyte maldevelopment and subfertility. Overall. this study uncovered that iron overload modulated the follicular microenvironment and generated a deleterious effect on female infertility via ROS/HIF-1α/FSHR signaling. These results might provide potential implications for future clinical risk management of patients with endometrioma and hemopathy.

A Validated Model for Individualized Prediction of Live Birth in Patients With Adenomyosis Undergoing Frozen-Thawed Embryo Transfer.

Purpose: This study aimed to develop a predictive tool for live birth in women with adenomyosis undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment. Methods: A total of 424 patients with adenomyosis who underwent frozen-thawed embryo transfer (FET) from January 2013 to December 2019 at a public university hospital were included. The patients were randomly divided into training (n = 265) and validation (n = 159) samples for the building and testing of the nomogram, respectively. Multivariate logistic regression (MLR) was developed on the basis of clinical covariates assessed for their association with live birth. Results: In total, 183 (43.16%) patients became pregnant, and 114 (26.88%) had a live birth. The MLR showed that the probability of live birth was significantly correlated with age [odds ratio (OR), 3.465; 95% confidence interval (CI), 1.215-9.885, P = 0.020], uterine volume (OR, 8.141; 95% CI, 2.170-10.542; P = 0.002), blastocyst transfer (OR, 3.231; 95% CI, 1.065-8.819, P = 0.023), twin pregnancy (OR, 0.328; 95% CI, 0.104-0.344, P = 0.005), and protocol in FET (P < 0.001). The statistical nomogram was built based on age, uterine volume, twin pregnancy, stage of the transferred embryo, and protocol of FET, with an area under the curve (AUC) of 0.837 (95% CI: 0.741-0.910) for the training cohort. The AUC for the validation cohort was 0.737 (95% CI: 0.661-0.813), presenting a well-pleasing goodness-of-fit and stability in this model. Conclusions: This visual and easily applied nomogram built on the risk factors of live birth in patients with adenomyosis provides useful and precise information for physicians on individualized decision-making during the IVF/ICSI procedure.

Ovarian Endometrioma Negatively Impacts Oocyte Quality and Quantity But Not Pregnancy Outcomes in Women Undergoing IVF/ICSI Treatment: A Retrospective Cohort Study.

Purpose: To determine the impact of ovarian endometrioma per se on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes. Methods: This retrospective study was conducted using two groups. The endometrioma group consisted of 862 women with infertility who had ovarian endometriomas and underwent their first ovarian stimulation for IVF/ICSI treatment between January 2011 to December 2019 at a public university hospital. A non-endometrioma comparison group, comprising 862 women with other infertility factors, was matched according to maternal age, body mass index (BMI), and infertility duration. Ovarian reserve and response and IVF/ICSI and pregnancy outcomes between the two groups were analyzed. Multivariate logistic regression (MLR) analysis was conducted on the basis of clinical covariates assessed for their association with live birth. Results: The results showed that significantly lower antral follicle count (AFC), anti-Müllerian hormone (AMH), ovarian sensitivity index (OSI), oocyte maturation and fertilization rates, blastocyst rate, number of oocytes retrieved, and available embryos were found in women with endometrioma compared with the control, respectively (P < 0.05). The cumulative live birth rate per patient in women with endometrioma was lower than that of women without endometrioma (39.32% vs. 46.87%, P = 0.002). In women with endometrioma, those who underwent surgical intervention prior to IVF/ICSI treatment had higher maturation (86.03% vs. 83.42%, P = 0.003), fertilization (78.16% vs. 74.93%, P = 0.004), and top-quality embryo rates (42.94% vs. 39.93%, P = 0.097) but had fewer oocytes retrieved (8.01 ± 5.70 vs. 9.12 ± 6.69, P = 0.013) than women without surgery. However, live birth rates were comparable between women with endometrioma and women in the control group, regardless of whether they had a prior history of ovarian surgery. MLR analysis showed no correlation between endometrioma per se and live birth after being adjusted for number of top-quality embryos transferred and stage of embryo transfer. Conclusions: The data from this study supported the conclusion that ovarian endometrioma negatively impacts oocyte quality and quantity, but not overall pregnancy outcomes, in women undergoing IVF/ICSI treatment. Endometrioma lowers the cumulative live birth rate by decreasing the number of embryos. Surgical excision of endometrioma prior to IVF/ICSI can partly improve oocyte maturation and fertilization rates but not pregnancy outcomes.

Role of the total progressive motile sperm count (TPMSC) in different infertility factors in IUI: a retrospective cohort study.

OBJECTIVE: The objective of this retrospective cohort study was to explore the optimal range of the total progressive motile sperm count (TPMSC) for live birth in couples with varying infertility diagnosis undergoing intrauterine insemination (IUI) in a university-affiliated teaching hospital. METHODS: A total of 2647 couples and 5171 IUI cycles were included between January 2015 and December 2018. Of those, 1542 cycles were performed due to unexplained infertility, 1228 cycles due to anovulation, 1120 cycles due to mild male factor infertility and 122 cycles due to mild endometriosis. The primary outcome measure was live birth rate (LBR). The secondary outcome measure was clinical pregnancy rate (CPR). RESULTS: The CPR and LBR were highest in patients with a diagnosis of anovulation compared with the other three groups of patients. The CPR and LBR in patients with unexplained, mild male factor and mild endometriosis were comparable. For the patients with mild male factor infertility, the CPR with prewash TPMSC of >75.0 M and postwash TPMSC of 65.10 M was above 10%, statistically significantly higher than other quartiles of TPMSC (p<0.05). The LBR with postwash TPMSC of >65.10 M was statistically significantly higher than other groups (p<0.05). However, in patients with unexplained infertility, the CPR and LBR were not statistically different in quartiles of TPMSC, being less than 10%. Overall, there was only one clinical pregnancy and no live birth in patients >40 years of age. CONCLUSIONS: In conclusion, the infertility diagnosis plays a significant role for the patient undergoing IUI. Thus, the anovulatory patients benefitted most from IUI, irrespective of TPMSC. For patients with unexplained infertility, TPMSC does not affect the success rate of IUI. Overall,female patients more than 40 years old should not be referred to IUI.

Ultra-Long GnRH Agonist Protocol During IVF/ICSI Improves Pregnancy Outcomes in Women With Adenomyosis: A Retrospective Cohort Study.

Objective: This study aimed to compare the ultra-long gonadotropin-releasing hormone agonist (GnRH-a) protocol and the long GnRH-a protocol during in vitro fertilization (IVF) or intracytoplasmic sperm (ICSI) treatment on fertility outcomes in women with adenomyosis. Materials and Methods: This study was a retrospective cohort study. From January 2011 to May 2018, a total of 371 fresh IVF/ICSI cycles were included. Among the cycles included, 237 cycles of 212 women underwent the ultra-long GnRH-a protocol, while 134 cycles of 116 women underwent the long GnRH-a protocol. The rates of implantation, clinical pregnancy per embryo transfer, live birth, and early miscarriage were estimated between the compared protocols. Results: In the study, the early miscarriage rate in women undergoing the ultra-long GnRH-a protocol was significantly lower than those undergoing the long GnRH-a protocol (12.0% versus 26.5%, p = 0.045), whereas the differences in the rates of biochemical pregnancy, implantation, clinical pregnancy, and live birth in women between the two groups showed no statistical significance. The pregnancy outcomes were also sub-analyzed according to the adenomyotic region (diffuse and focal). As for diffuse adenomyosis, the rates of clinical pregnancy and live birth in women undergoing the ultra-long GnRH-a protocol were significantly higher than those undergoing the long GnRH-a protocol (55.3% versus 37.9%, p = 0.025; 43.4% versus 25.9%, p = 0.019, respectively). However, pregnancy outcomes showed no difference between the two protocols in women with focal adenomyosis. Conclusions: The ultra-long GnRH-a protocol during IVF/ICSI improves pregnancy outcomes in women with adenomyosis, especially in women with diffuse adenomyosis when compared with the long GnRH-a protocol.

C-reactive protein and risk of ovarian cancer: A systematic review and meta-analysis.

BACKGROUND: Although several studies have suggested an association between elevated C-reactive protein (CRP) and ovarian cancer risk, others have yielded contradictory results. To address this issue, we conducted a meta-analysis. METHODS: Studies were identified by searching PubMed and EMBASE up to July 2017 without language restrictions. Six case-control studies and 1 cohort study were included, including 1898 ovarian cancer cases. Pooled risk estimates were generated by using the fixed-effect model or the random-effect model based on the heterogeneity between studies. RESULTS: As our data shown, the combined ORs were 1.04 (95%CI: 0.90-1.21) and 1.34 (95% CI: 1.06-1.70) for the risk in the second and third tertiles of CRP with those in the bottom tertile, respectively. Subgroup analysis showed that with respect to the top tertile of CRP level, the association was significant for studies obtaining CRP from serum (OR=1.99; 95% CI: 1.30-3.07), conducted in the USA (OR = 1.41; 95% CI: 1.15-1.72), using high-sensitivity immunotubidimetric assay (OR = 1.37; 95% CI: 1.14-1.64), using Hs-CRP (OR = 1.46; 95% CI: 1.21-1.75) and with follow-up period longer than 10 years (OR = 1.41; 95% CI: 1.18-1.70). CONCLUSION: Collectively, our findings propose that serum CRP levels may serve as an indicator of ovarian cancer risk. Further studies are needed to definitively identify the role of CRP in the etiology of ovarian cancer.

Predictive value of serum ß-hCG for early pregnancy outcomes among women with recurrent spontaneous abortion.

OBJECTIVE: To examine peak serum levels of the ß-subunit of human chorionic gonadotropin (ß-hCG) for prediction of early pregnancy outcomes among women with recurrent spontaneous abortion (RSA). METHODS: In a retrospective study, the medical records of pregnant women with a history of RSA treated at Sun Yat-sen Memorial Hospital, China, between January 2011 and July 2013 were reviewed. Serum ß-hCG had been measured twice weekly from 5 to 13weeks of pregnancy, and pregnancy was monitored by transvaginal ultrasonography to 13(+6)weeks. Optimal cutoff for peak ß-hCG level was determined by receiver operator characteristic curve analysis and Youden index. Women were divided into four groups on the basis of optimal peak ß-hCG cutoff and pregnancy outcome (pregnancy at 13weeks or spontaneous abortion). Peak ß-hCG levels and length of pregnancy at this peak were examined. RESULTS: Overall, 1240 patients were included. The optimal cutoff value of peak ß-hCG was 88 468IU/L, with a sensitivity, specificity, positive predictive value, and negative predictive value for successful pregnancy of 95.6%, 88.0%, 95.6%, and 89.0%, respectively. A faster rise in ß-hCG, higher peak ß-hCG, and longer pregnancy length at peak ß-hCG were associated with successful early pregnancy. CONCLUSION: A cutoff value of serum ß-hCG of 88 000IU/L could be used to predict early pregnancy outcomes for women with a history of RSA.