IVF-ET Outcome Research Articles

Very Early Pregnancy Loss: The Role of PM2.5 Exposure in IVF-ET Outcomes

Very Early Pregnancy Loss: The Role of PM_2.5 Exposure in IVF-ET Outcomes

P-299 The influence of ovarian endometriomas surgery or not and the iron overload in follicular fluid on the outcome of IVF-ET

Abstract Study question To investigate the influence of ovarian endometriomas(OEM) surgery or not on the outcome of in vitro fertilization and embryo transfer. Summary answer Laparoscopic surgery can not significantly improve the outcome of IVF-ET in OEM patients, but may decrease the ovarian reserve. What is known already Despite the great advantages of ovarian endometriomas surgery treatment in endometriosis-linked infertility, the impact of laparoscopic cystectomy on outcomes of infertility management with ART is controversial. Numerous mechanisms have been proposed in an effort to delineate the multifaceted pathophysiology that induces impairment of reproductive dynamics in patients with OEM. Reactive oxygen species, dysregulation of the immune system and iron overload constitute the crucial mechanisms that detrimentally affect oocyte and embryo developmental potential. Study design, size, duration This study retrospectively included 882 cycles in our reproductive center from January 2018 to December 2020, and the patients were divided into operation group (n = 386) and OEM group (n = 496) according to whether they underwent laparoscopic cystectomy before IVF-ET. Participants/materials, setting, methods The baseline data of age, infertility duration, basic FSH, AFC, and BMI were used as matching factors, and Propensity score matching was carried out according to the sample ratio of 1:1, and 327 cycles in the operation group and 327 cycles in the OEM group were finally included. Follicular fluid was collected under ultrasound guidance during oocyte retrieval. A total of 74 follicular fluid samples meeting the study conditions were collected. Main results and the role of chance (1)The clinical pregnancy rate of fresh embryo transfer cycle in the OEM group was significantly higher than that in the operation group (77.4% Vs 52.9%), and the difference was statistically significant (P = 0.039). There was no significant difference in pregnancy outcome in frozen embryo transfer cycle (P > 0.05). (2) The results of Multi-factor logistic regression model showed the clinical pregnancy rate of patients in the OEM group was 3.048 times than that of patients in the operation group in fresh cycle, and the difference was significant (OR 3.029 95%CI 1.017-9.018, P = 0.047), while early abortion and live birth pregnancy outcomes were not significantly affected in both groups. For the frozen embryo transfer cycle, there were no significant effects on clinical pregnancy, early abortion and live birth pregnancy outcomes in both groups. (3) There was no significant difference in follicular fluid iron concentration between OEM group and control group(11.53±3.38 Vs 12.18±4.37μg/dl, P = 0.112). The concentration of ferritin in follicle fluid in OEM group (57.38±139.90) was significantly higher than that in control group (24.88±13.76 μg/ml), the difference was statistically significant (P = 0.032). Limitations, reasons for caution The present study being of a retrospective and monocentric study, may not come to a very convincing conclusion, and some unknown biases might still exist due to possible underestimation of some confounders. Wider implications of the findings Collectively, our results indicate that laparoscopic ovarian cystectomy couldn’t significantly improve the IVF-ET outcomes in patients with OEM, but rather increased the risk of reduced ovarian reserve function. Ovarian reserve function was the main factor affecting the IVF-ET outcomes for infertile patients with OEM. Trial registration number /

#304 : Comparing GnRH Agonist and GnRH Antagonist Protocols for IVF-ET Outcomes in Patients with Endometriosis: A Meta-Analysis

Background and Aims: Endometriosis is known to have detrimental effects on fertility, but there is no consensus on the optimal stimulation protocol for IVF-ET in patients with endometriosis. The study aimed to compare the IVF outcomes of gonadotropin-releasing hormone (GnRH) agonist protocols versus antagonist protocols in patients diagnosed with endometriosis. Method: We performed a meta-analysis of studies that compared IVF outcomes of GnRH agonist versus antagonist protocols in patients with endometriosis. Through literature search, we retrieved 222 articles, and the last search date was April 7, 2023. Among them, six studies which met inclusion criteria were eligible for final analysis. The primary outcome was clinical pregnancy. Random effects and fixed effects models were applied according to I2 statistics. Results: The use of GnRH agonist was associated with higher clinical pregnancy rate (Odds ratio (OR) 1.61, 95% CI 1.35–1.93, 6 studies, [Formula: see text]<0.00001, I2=16%), higher live birth rate (OR 1.75, 95% CI 1.32–2.33, 3 studies, [Formula: see text]<0.0001, I2=12%), and similar miscarriage rate. The total dose of gonadotropin did not differ between the two methods, but the GnRH agonist protocol had a longer duration of stimulation (WMD 1.34, 95% CI 0.44–2.24, 5 studies, I2=98%), retrieved more oocytes (WMD 2.23, 95% CI 0.58–3.88, 3 studies, [Formula: see text]=0.0008, I2=97%), more MII oocytes (WMD 2.81, 95% CI 2.34–3.28, 3 studies, [Formula: see text]<0.00001, I2=0), and more embryos (WMD 1.90, 95%CI 1.13–2.67, 3 studies, [Formula: see text]<0.00001, I2=68%). Conclusion: Patients with endometriosis may benefit from using GnRH agonist protocol in the IVF-ET cycle, as it may be associated with a higher clinical pregnancy rate and live birth rate. Even though the stimulation duration is longer, more oocytes, mature oocytes, and embryos may be expected. Although the findings of this study may be potentially beneficial for clinicians, it is crucial to conduct additional randomized prospective trials with larger cohorts to further validate the results.

Effects of acupuncture on pregnancy outcomes in women undergoing in vitro fertilization: an updated systematic review and meta-analysis.

To evaluate the effects of acupuncture on IVF-ET outcomes. Digital databases, including Pubmed, Embase, the Cochrane Library, the Web of Science and ScienceDirect, were searched from their inception to July 2022. The MeSH terms we used included: acupuncture, in vitro fertilization, assisted reproductive technology and randomized controlled trial. The reference lists of relevant documents were also searched. The biases of included studies were assessed by the Cochrane Handbook 5.3. The major outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR). The pregnancy outcomes reported in these trials were pooled and expressed as risk ratios (RR) with 95% confidence interval (CI) in the Review Manager 5.4 meta-analysis software. Heterogeneity of the therapeutic effect was evaluated with a forest plot analysis. Publication bias was assessed by a funnel plot analysis. Twenty-five trials (a total of 4757 participants) were included in this review. There were no significant publication biases for most of the comparisons among these studies. The pooled CPR (25 trials) of all the acupuncture groups (43.6%) was significantly higher than that of all the control groups (33.2%, P < 0.00001), and the pooled LBR (11 trials) of all the acupuncture groups (38.0%) was significantly higher than that of all the control groups (28.7%, P < 0.00001). Different acupuncture methods (manual acupuncture, electrical acupuncture and transcutaneous acupoint electrical stimulation), acupuncture time (before or during the time of controlled ovarian hyperstimulation and around the time of embryo transfer), and acupuncture courses (at least 4 sessions and less than 4 sessions) have respectively positive effects on IVF outcomes. Acupuncture can significantly improve CPR and LBR among women undergoing IVF. Placebo acupuncture can be a relatively ideal control measure.

Rapid and non-invasive diagnostic techniques for embryonic developmental potential: a metabolomic analysis based on Raman spectroscopy to identify the pregnancy outcomes of IVF-ET.

The non-invasive and rapid assessment of the developmental potential of embryos is of great clinical importance in assisted reproductive technology (ART). In this retrospective study, we analyzed the metabolomics of 107 samples provided by volunteers and utilized Raman spectroscopy to detect the substance composition in the discarded culture medium of 53 embryos resulting in successful pregnancies and 54 embryos that did not result in pregnancy after implantation. The culture medium from D3 cleavage-stage embryos was collected after transplantation and a total of 535 (107 × 5) original Raman spectra were obtained. By combining several machine learning methods, we predicted the developmental potential of embryos, and the principal component analysis-convolutional neural network (PCA-CNN) model achieved an accuracy rate of 71.5%. Furthermore, the chemometric algorithm was used to analyze seven amino acid metabolites in the culture medium, and the data showed significant differences in tyrosine, tryptophan, and serine between the pregnancy and non-pregnancy groups. The results suggest that Raman spectroscopy, as a non-invasive and rapid molecular fingerprint detection technology, shows potential for clinical application in assisted reproduction.

P-334 Transcriptomic patterns in early-secretory and mid-secretory endometrium in a natural menstrual cycle immediately before in vitro fertilization and embryo transfer

Abstract Study question To evaluate endometrial transcriptomic patterns in early-secretory phase (ESP) and mid-secretory phase (MSP) in a natural menstrual cycle before IVF-ET Summary answer Endometial ranscriptomic patterns in ESP and MSP immediately before IVF-ET appear to differ according to IVF-ET outcome, which may be implicated in endometrial receptivity. What is known already Biologic processes and molecular participants in the transition from ESP to MSP endometrium underscore the complex events in preparing for embryo implantation. Previously reported genes with altered expression during endometrial transition from the ES phase to the MS phase were frequently involved in ion binding, cell cycle regulation, transport of signaling proteins, or immune modulation. Although several studies have compared gene expression in the receptive phase and pre-receptive phases in an attempt to identify a molecular signature characteristic of a receptive endometrium, a consensus has not been reached regarding the genes accounting for transcriptomic differences between phases. Study design, size, duration Differentially expressed genes (DEGs) in the MSP, compared to the ESP, were identified using NanoString nCounter data in both the pregnant and non-pregnant groups. Participants/materials, setting, methods A total of 30 patients whose endometrial tissues were obtained in a natural menstrual cycle immediately before IVF-ET were included. Endometrial dating was histologically confirmed as ESP (cycle day 16 to 18) or MSP (cycle day 19 to 21) according to Noyes criteria. The patients were divided into two groups depending on IVF-ET outcome: pregnant (n = 14; 7 in ESP and 7 in MSP) or non-pregnant (n = 16; 8 in ESP and 8 in MSP). Main results and the role of chance A total of 14 DEGs were identified when comparing the ES phase and MS phase endometrium in the pregnant group. A total of 12 DEGs were identified when comparing the ES phase and MS phase endometrium in the non-pregnant group Nine genes were upregulated in the MS phase endometrium, compared to the ES phase endometrium, in both the pregnant and non-pregnant groups: adrenoceptor alpha 2A (ADRA2A), interleukin 1 receptor-associated kinase 2 (IRAK2), a disintegrin and metalloproteinase with thrombospondin repeats 15 (ADAMTS15), serpin family E member 1 (SERPINE1), integrin subunit beta 3 (ITGB3), transmembrane protein 252 (TMEM252), huntingtin associated protein 1 (HAP1), C2 calcium-dependent domain containing 4A (C2CD4A), and integrin subunit alpha 2 (ITGA2). Four genes were upregulated in the MS phase endometrium, compared to the ES phase endometrium, only in the pregnant group: TMEM37, galactosidase beta 1 like 2 (GLB1L2), Rho family GTPase 3 (RND3), and cytochrome P450 family 24 subfamily A member 1 (CYP24A1). One gene (ADAMTS8) was downregulated and one gene (monoamine oxidase A [MAOA]) was upregulated in the MS phase endometrium, compared to the ES phase endometrium, only in the non-pregnant group. Limitations, reasons for caution Firstly, since our sample size was relatively small, our results should be considered preliminary. Secondly, because endometrial tissue samples wee not obtained in IVF-ET cycle, they may not reflect changes in an actual pregnancy cycle.Thirdly, there may have been embryonic effects on implantation that were not accounted for. Wider implications of the findings TMEM37, GLB1L2, RND3, and CYP24A1 were upregulated only in the pregnant group; ADAMTS8 was downregulated while MAOA was upregulated only in the non-pregnant group.These novel DEGs, which have not been previously studied, may have functional significance during the WOI and serve as potential biomarkers of endometrial receptivity. Trial registration number not applicable

The effect of large follicle puncture and aspiration on the outcomes of IVF-ET in patients with asynchronized follicles under the long GnRH-a protocol: a retrospective cohort study

ObjectiveThis retrospective study aimed to explore whether puncturing and aspirating asynchronized large follicles during long GnRH-a protocol COH impacted IVF-ET outcomes.MethodsA total of 180 patients with asynchronized follicles during long GnRH-a protocol COH were retrospectively analyzed. They were divided into a puncture group, Group 1 (n = 81), and a non-puncture group, Group 2 (n = 99), according to whether puncture and aspiration were performed on the prematurely developing large follicles. The data of the selected patients were statistically analyzed to assess the effect of large follicle puncture and aspiration during ovulation induction on the final pregnancy results. In addition, we tentatively divided these 180 patients into either Group A (DF ≤ 14 mm) or Group B (DF > 14 mm) according to whether the diameter of the dominant large follicles (DF) exceeded 14 mm at the time of appearance. These two groups were then further divided into four subgroups: Subgroup A1 (DF ≤ 14 mm, patients underwent large follicle puncture), Subgroup A2 (DF ≤ 14 mm, patients did not undergo large follicle puncture), Subgroup B1 (DF > 14 mm, patients underwent large follicle puncture), and Subgroup B2 (DF > 14 mm, patients did not undergo large follicle puncture) based on whether large follicle puncture and aspiration were performed or not, aiming to compare the effects of large follicle puncture and aspiration on the clinical outcomes of patients with dominant large follicles at different time points.ResultsGroup 1 exhibited significantly higher oocyte maturation rate (92.3% vs. 88.9%, P = 0.009) and high-quality embryo rate (75.2% vs. 65.7%, P = 0.007) compared with Group 2. No differences were observed in the number of oocytes retrieved, 2PN fertilization rate, clinical pregnancy rate, abortion rate, and live birth rate between the two groups (P > 0.05). When the dominant large follicles' diameter was ≤ 14 mm, the final oocyte maturation rate (92.7% vs. 88.1%, P = 0.023), high-quality embryo rate (72.9% vs. 61.8%, P = 0.047) and live birth rate (54.5% vs. 31.9%, P = 0.043) of Subgroup A1 were significantly higher than those of Subgroup A2. In contrast, when the dominant large follicles' diameter was > 14 mm, no statistical difference was observed in all data.ConclusionsLarge follicle puncture and aspiration in long GnRH-a protocol COH could improve the oocyte maturation rate and high-quality embryo rate in patients with asynchronized follicles. However, clinical pregnancy and live birth rates were not significantly improved. In addition, when the dominant follicles' diameter did not exceed 14 mm, large follicles puncture and aspiration significantly improved the patient's oocyte maturation rate, high-quality embryo rate and live birth rate.

Elective egg freezing patients may benefit from increasing the maximal daily gonadotropin dose above 300IU

ObjectiveNowadays, patients attempting social/elective egg freezing has spread globally. Ovarian stimulation (OS) with high daily gonatotropin doses, are commonly offered to this group of patients, aiming to achieve the maximal oocytes cohort with minimum IVF cycle attempts. We aim to assess the IVF-ET outcome, and specifically the oocyte yield, of patients undergoing two successive IVF cycle attempts for elective egg freezing (EEF), and whether changing the daily gonadotropin dose in the second IVF cycle attempt, affect the outcome.Patients and methodsAll women admitted to our IVF unit for social/EEF, who underwent 2 consecutive IVF cycle attempts, with only those who used in the first attempt a starting daily gonadotropin dose of 300 IU were included. Ovarian stimulation characteristics, duration of OS, number of retrieved oocytes, number of mature oocytes were assessed and compared between the 1st and the 2nd IVF cycle attempts, and between the different daily gonadotropin doses and the oocyte yields in the 2nd cycle attempt (increase, decrease or no change).Main outcome measuresOocytes and mature oocytes yield in the 2nd as compared to the 1st IVF cycle attempt.ResultsA reduced oocyte yield in the 2nd cycle attempt was observed in those who highly responded in the 1st attempt, regardless the daily dose in the 2nd cycle attempt (whether it was increased, no change and decreased). Moreover, the proportion of patients with same or more oocytes in the 2nd IVF cycle attempt was significantly lower in patients with high peak E2 levels, compared to those with peak E2 levels < 9175 pmol/L. Among patients with high peak E2 (> 9175 pmol/L), those who achieved a lower oocytes yield in the 2nd IVF cycle attempt had lower basal Day-3 FSH/LH ratio (1.5 + 0.5 vs 1.8 + 0.8, p < 0.03) and higher oocyte (range: 7–28, median:10; vs range: 2–15, median:7) and mature oocytes yields. With a cut-off of 9 oocytes, 78.8% of those with > 9 oocytes and 61.8% of those with < 9 oocytes will achieve lower/higher oocytes yield in the 2nd IVF cycle attempt, respectively.ConclusionsOvarian stimulation with high daily gonatotropin doses (300 IU) should be offered to patients attempting social/EEF. Moreover, in their 2nd IVF cycle attempt, those with high peak E2 (> 9175 pmol/L) in the 1st attempt, and basal Day-3 FSH/LH ratio < 1.5 and/or more than 9 oocytes retrieved, should receive same OS protocol with no change in the daily gonadotropin dose.

A predictive model for first-trimester pregnancy inception after IVF-ET based on multimodal ultrasound evaluation of endometrial receptivity

BackgroundIn-vitro fertilization-embryo transfer (IVF-ET) is a commonly used assisted reproductive technology. Its success depends on many factors, including endometrial receptivity. Endometrial receptivity can be evaluated by ultrasound, endometrial biopsy, and magnetic resonance imaging. Compared with the latter two methods, ultrasound has the advantages of wide availability, non-invasiveness, and low cost. Three-dimensional (3D) ultrasound imaging examines endometrial thickness, morphology, and blood vessels, which are associated with the success of embryo implantation. However, there are no reports of endometrial receptivity assessment by 3D ultrasound. Therefore, we aimed to evaluate endometrial receptivity using 3D ultrasound and construct a predictive model for first-trimester pregnancy inception following IVF-ET.MethodsWe performed a prospective observational study on infertile women who underwent IVF-ET between December 2019 and February 2021. These women had 3D ultrasound evaluations, measuring endometrial thickness, volume, pattern, morphology, peristalsis, uterine artery blood flow index, sub-endometrial blood flow index, and distribution pattern. We recorded the occurrence of first-trimester pregnancies in these women. Using Akaike information criterion (AIC) and backward stepwise regression, a first-trimester pregnancy prediction model was constructed based on the minimum AIC value and validated internally and externally.Results111 women were enrolled, with 103 included in the analysis. Univariate and multiple logistic regression analyses showed that endometrial thickness and vascularization flow index (VFI) were independent factors associated with the occurrence of a pregnancy. The final prediction model corresponding to the minimum AIC value (65.166) was Y = − 6.131–0.182endometrial thickness + 0.542endometrial volume + 4.374VFI + 0.132age. In the test set, modeling cohort, and external validation cohort, the model showed satisfactory differentiation, with C index of 0.841 (95%CI 0.699–0.817), 0.727 (95%CI 0.619–0.815), and 0.745 (95%CI 0.671–0.840), respectively. The Hosmer–Lemeshow goodness of fit tests reported P = 0.865, 0.139, and 0.070, respectively, indicating a high agreement with the actual IVF-ET outcome. This model reached the highest diagnostic efficiency (sensitivity 88.9%, specificity 75%, Youden index 0.639) at a diagnostic cut-off value of ≥ 0.360.ConclusionsThe predictive model based on endometrial receptivity evaluations by 3D ultrasound had high diagnostic efficiency and could be a simple and effective tool to predict first-trimester pregnancy inception after IVF-ET.

The Effect of Age on IVF-ET Outcome in Infertile Patients with PCOS Based on Tiangui Theory in Chinese Medicine.

Objective Our aim was to investigate the effect of age on the outcome of IVF-ET and ICSI in infertile PCOS patients under the guidance of Tiangui theory in traditional Chinese medicine. Method This was a retrospective analysis of 532 infertile women with PCOS and 1,392 women with infertility due to tubal factors as the controls. All of the participants were divided into different age groups-aged 20–28 years, 29–35 years, and ≥36 years-according to the stages of female reproductive development in Tiangui theory as described in the Canon of Internal Medicine-Treatise of Ancient Natural Truth. We explored the effect of age on controlled ovarian hyperstimulation (including the initial dosage and duration of Gn and the estradiol level on the day of human chorionic gonadotropin administration); the numbers of retrieved oocytes, 2PN zygotes, and embryos; and the rates of fertilization, clinical pregnancy, abortion, live birth, and OHSS incidence. Results Compared to controls, the maximum follicular diameter and the numbers of follicles with d ≥ 20 mm, retrieved oocytes, and 2PN zygotes were greater in the PCOS group with age >28 years (p < 0.05). The abortion rate of PCOS patients with age ≤28 years was higher than that of the controls. All PCOS groups and the control group showed reduced numbers of retrieved oocytes and live births with age. The difference in age was not significant in the PCOS groups but was significant in the control group (p < 0.05), and the trend in the PCOS groups was more gradual. Conclusion The fertility of all subjects decreased with age, but PCOS patients decreased more slowly than in controls at the same age, which verified the applicability of the guiding principles of Tiangui theory in the clinic.

P-693 IVF outcome in patients with thyroid disease

Abstract Study question What is the thyroid disease rate in IVF patients and how does it affect their IVF outcome? Summary answer The thyroid disease rate was 19,5%, mostly of inflammatory origin. IVF outcome in these patients was similar to controls, but coexisting endometriosis rate was higher. What is known already Thyroid disease is the most common endocrine disorder in females of reproductive age. It is estimated that 20% of infertile females has history of thyroid disease. Thyroid hormones importantly impact fertility, acting directly on oocytes, sperm and embryo during fertilization, implantation and placentation, regulating estrogen and androgen metabolism as well as the menstrual cycle. The most common causes of thyroid disfunction are autoimmune disorders. The prevalence of thyroid autoimmunity among women undergoing IVF treatment is higher compared to the general population. Women with thyroid autoimmunity have higher risk of miscarriage, preterm birth and it may impact the IVF-ET outcome. Study design, size, duration It was a single center trial at the Division of Obstetrics and Gynecology, Department of Human Reproduction in the University Medical Centre of Ljubljana, Slovenia. The study included women undergoing their first IVF treatment in a one-year period. Participants/materials, setting, methods A total of 226 women undergoing their first IVF treatment were included. In the first part of our study, Patient characteristics and IVF outcome according to different TSH serum levels (&amp;lt; 0,59 mE/L, 0,59 - 2,5 mE/L, 2,5 - 4,23 mE/L ter &amp;gt; 4,23 mE/L) were analysed. In the second part of the study, we compared patient characteristics and IVF outcome in patients with and without thyroid disease. Main results and the role of chance The average age was 33 ± 4,7 years, the average BMI was 24±4,9 kg/m2. Three percent of women had TSH levels &amp;lt;0,59 mE/L, 74% had TSH levels 0,59-2,5 mE/L,18% had TSH levels 2,5-4,23 mE/L and 6% had TSH levels &amp;gt;4,23 mE/L. The obesity rate (BMI&amp;gt;30 kg/m2) was significantly different in all four groups of patients with the highest rate in the group of TSH 2,5-4,23 mE/L. Thyroid disease was found in 19,5% of patients (thyroid autoimmunity 18%, Hashimoto's thyroiditis 7,5% of patients). The thyroid disease rate was significantly different in all four groups with highest rate in group having TSH &amp;gt;4,23 mE/L and the lowest rate in group having TSH 0,59-2,5 mE/L. Endometriosis was diagnosed in 22% of patients with highest rate in patients having highest TSH levels. There was no correlation between patient characteristics and reproductive history (age, irregular menstrual cycle, dysmenorrhea, pregnancy, spontaneous abortion, recurrent abortion, FSH and LH serum levels) and TSH levels or preexisting thyroid disease. There were no significant differences in the IVF outcome (numbers of retrieved oocytes, immature oocytes and number of embryos) according to TSH levels or preexisting thyroid disease. Thyroid disease rate was significantly higher in patients with endometriosis. Limitations, reasons for caution Our study limitation is a smaller sample size that may affect our results, specifically the differences in the IVF outcome. There was no statistical difference in miscarriage and recurrent miscarriage rate in women with thyroid disease and women with normal thyroid function. Wider implications of the findings Our study gives an insight to the characteristics of women with thyroid disease undergoing IVF treatment in our facility, although the differences were statistically insignificant. As a secondary outcome we discovered a statistically significant correlation of endometriosis and inflammatory thyroid disease, which is rarely mentioed in the literature. Trial registration number not applicable

Effect of Prolonged GnRH Agonist Therapy Prior to Frozen Embryo Transfer on IVF-ET Outcome in Patients with and without Endometrioma Surgery

Objective: It remains to be clarified whether prolonged Gonadotrophin-Releasing Hormone agonist (GnRHa) administration before frozen embryo transfer to patients with and without endometrioma resection improves reproductive outcome. This study was designed to investigate freeze-all cycles with subsequent prolonged GnRHa administration in patients with and without endometrioma surgery. Method: A total of 164 patients with complaints of infertility and diagnosed with endometrioma were included in this case controlled study. Endometrioma resection was performed in 65 out of 164 women and then Controlled Ovarian Stimulation (COS) was performed (Group 1). Fresh embryos were transferred to 40 of 65 patients who underwent endometrioma surgery. Embryos were vitrified in 25 patients and administered leuprolide acetate 3.75 mg for 3 months. The remaining 99 patients were referred directly to the COS without any surgery for endometrioma (Group 2). While fresh-ET was applied to 49 of 99 cases, embryos were frozen in the remaining 50 cases. Subsequently they were administered leuprolide acetate 3.75 mg for 3 months. Primary outcome was Clinical Pregnacy Rates (CPR), Ongoing Pregnancy Rates (OPR), and Live Birth Rates (LBR). Results: No significant difference was found between the operated and non- operated groups in terms of CPR, OPR and LBR between patients who received fresh-ET. While there was no significant difference in CPR and OPR in operated and non-operated groups who underwent frozen-ET, LBRs were found to be significantly higher in patients who were not operated (p&lt;0.01). Making fresh-ET or frozen-ET in patients who underwent endometrioma surgery did not significantly affect CPR, OPR and LBR. Making frozen-ET in patients who did not undergo surgery significantly increased both CPR (p &lt;0.02) and OPR (p&lt;0.03). Conclusion: Prolonged use of GnRH agonist treatment before frozen-ET in patients without endometrioma surgery resulted in significantly higher clinical and ongoing pregnancy rates than did patients with endometrioma surgery.

Effect of traditional Chinese medicine formula Guilu Xian on in vitro fertilization and embryo transfer outcome in older women with low prognosis: study protocol for a prospective, multicenter, randomized double-blind study

IntroductionIn recent years, the prevalence of infertility has significantly increased and has become a global reproductive health problem. The female ovarian reserves have been shown to decrease progressively with an increase in age. Besides, the rate of embryo implantation and clinical pregnancy also decreases. Traditional Chinese medicine has been widely applied in assisted reproductive technology. It is reported to have a significant influence on improving the quality of oocytes, improving endometrial receptivity, increasing clinical pregnancy rate, reducing pregnancy-related complications, etc. Therefore, this study will investigate the effect of Guilu Xian, a traditional Chinese medicine formula on IVF-ET outcome in older women with low prognosis.Methods and analysisThis trial is a prospective, multicenter, randomized double-blind clinical trial. A total of 120 infertile patients with low prognosis and receiving IVF or ICSI in 3 public hospitals in China will be randomly divided into two parallel groups: Guilu Xian group (n = 60) and placebo group (n = 60). Patients in both groups will be treated with antagonist regimens to promote ovulation, and all the patients will be required to take the medication from the 2nd to 4th day of the menstrual cycle to the day of egg retrieval. A comparison of the total number of oocytes obtained, the fertilization rate, clinical pregnancy rate, embryo quality, embryo implantation rate, and early spontaneous abortion rate between the experimental group and the placebo group will be performed.Trial registrationChinese Clinical Trials Registry ChiCTR1900028255. Registered on 16 December 2019.

Effects of half-dose and full-dose GnRH antagonists on IVF-ET outcomes: a retrospective study

BackgroundGonadotropin-releasing hormone antagonist(GnRH-ant) has been shown to have a negative effect on endometrial receptivity. Therefore, the use of lower doses of GnRH-ant during controlled ovarian stimulation (COS) may improve endometrial receptivity and clinical pregnancy rate. However, the GnRH-ant dose is relatively flexible and there is no fixed requirement for guidance. In this retrospective study, we determined the effects of half-dose and full-dose GnRH-ant on IVF-ET outcomes.MethodsOf the 316 cycles in the 314 patients analyzed in this study, 149 received GnRH-ant half-dose (Group1), while 167 received GnRH-ant full-dose (Group2). The groups were further classified based on age and BMI. Age subgroups, were divided as age ≤ 35(subgroup A) and age > 35(subgroup B): 180 cycles in subgroup A (107 cycles in subgroup A1,73 cycles in subgroup A2), 136 cycles in subgroup B (42 cycles in subgroup B1,94 cycles in subgroupB2). The subgroups based on BMI were divided as BMI < 25 (subgroup C)and BMI ≥ 25 (subgroup D):208 cycles in subgroup C (94 cycles in subgroup C1,114 cycles in subgroup C2), 108 cycles in subgroup D (55 cycles in subgroup D1,53 cycles in subgroup D2).ResultsThe number of fertilized oocytes, superior-quality embryos, clinical pregnancy rate, and live birth rate differed significantly between the two groups. However, the number of retrieved oocytes and available embryos were significantly higher in Group 1 than Group 2 (8.17 ± 4.10 vs. 7.07 ± 4.05, 2.96 ± 2.03 vs. 2.52 ± 1.62, respectively,p<0.05). Differences between the age subgroups were not statistically significant. However, in the subgroups based on BMI, the fertilized oocytes, available embryos, the number of superior-quality embryos, and the live birth rate differed significantly between the four subgroups. The number of retrieved oocytes was higher in subgroup C1 than in subgroup C2 (8.24 ± 4.04 vs. 6.83 ± 3.92,p < 0.05), In addition, the clinical pregnancy rate was slightly higher in subgroup D1 than in subgroup D2(45.45 vs. 24.53%, P < 0.05).ConclusionsThe results showed that half-dose GnRH-ant was as effective as full-dose GnRH-ant for most patients. Moreover, half-dose GnRH-ant may be more suitable in patients with BMI greater than or equal to 25. The findings of this study need to be validated in a large sample RCT.Trial registrationRetrospectively registered.

Roles of miR-10a-5p and miR-103a-3p, Regulators of BDNF Expression in Follicular Fluid, in the Outcomes of IVF-ET.

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays critical roles in the physiological process of oocyte mature and IVF outcomes of patients with infertility. However, the regulation of BDNF expression in the microenvironment surrounding the oocyte is still unknown. We initially predicted some microRNA (miRNA) candidates targeting bdnf with a series of bioinformatics analysis tools to determine the underlying regulatory mechanisms of BDNF, particularly the effect of miRNAs on BDNF expression. Then, we assessed whether the expression of these 14 selected miRNAs was negatively associated with BDNF expression in follicular fluid (FF) samples obtained from mature (>18 mm) or immature (<15 mm) follicles. Finally, we used the candidate miRNAs, miR-103a-3p and miR-10a-5p, to further investigate the relationship between their expression in FF and the outcomes of infertile patients undergoing IVF–ET treatment. The results of the bioinformatics analysis revealed 14 miRNAs that might directly regulate BDNF expression and might have a close relationship with oocyte development. BDNF was expressed at significantly lower levels in FF from immature follicles than in FF from mature follicles, and only the expression of miR-103a-3p and miR-10a-5p was negatively correlated with BDNF expression in FF. Moreover, in another cohort of 106 infertile women undergoing IVF-ET treatment, miR-103a-3p or miR-10a-5p expression predicted the developmental status of the corresponding oocytes in which high expression of miR-103a-3p or miR-10a-5p resulted in a poor quality of embryo on days 3 and 5 during the IVF-ET treatment. In conclusion, our study is the first to show that miR-103a-3p or miR-10a-5p negatively affects the maturation of oocytes by regulating the expression of BDNF in human FF. Additionally, the expression levels of miR-103a-3p or miR-10a-5p in FF may predict the outcomes of IVF, which are helpful for improving embryo selection and consequently the IVF success rate in the clinic.

Follicular fluid estradiol is an improved predictor of in vitro fertilization/intracytoplasmic sperm injection and embryo transfer outcomes.

The present study is a clinical trial analyzing follicular fluid. The current study aimed to assess whether a correlation exists among estradiol (E2), anti-Mullerian hormone (AMH) and prokineticin 1 (PROK1) levels in the follicular fluid. A total of 81 infertile patients (53 with primary infertility and 28 with secondary infertility) who received routine in vitro fertilization (IVF) and embryo transfer (ET) or intracytoplasmic sperm injection at Yuhuangding Hospital (Yantai, China) were included in the present study. On the day of egg retrieval, follicular puncture and follicular fluid extraction were performed on patients using double lumen needles under the guidance of a vaginal ultrasound. In 77 cases, follicular fluid was collected from the follicle with the largest diameter. A total of 53 cases underwent ET and subsequent pregnancy outcomes were traced. Concentrations of E2, AMH and PROK1 in the single follicular fluid specimens were determined. The concentration of E2 in follicular fluid from the largest follicles in absolute pregnancy group was significantly lower than that in absolute non-pregnancy group. The concentrations of PROK1 and AMH in follicular fluid from the largest follicles in absolute pregnancy group were not significantly different from those in absolute non-pregnancy group. The concentration of E2 was associated with the dosage of gonadotropin, but was not associated with age, AMH and PROK1 levels in follicular fluid, fertilization rate or number of usable blastocysts. The area under curve revealed that E2 level in the follicular fluid exhibited a low predictive value for pregnancy outcome. The present study demonstrated that E2 level is a better predictor for the outcome of IVF-ET than AMH or PROK1 levels in the follicular fluid.

Extended doxycycline treatment versus salpingectomy in the management of patients with\xa0hydrosalpinx undergoing IVF-ET

BackgroundThe aim of this study was to determine whether the treatment with doxycycline before and after oocyte retrieval is as effective as salpingectomy in minimizing the detrimental effect of hydrosalpinx on the outcomes of IVF-ET.MethodsA retrospective analysis was done for the outcomes of the IVF-ET cycles of patients with hydrosalpinx who underwent laparoscopic salpingectomy prior to IVF cycle (n = 260) or were treated with extended doxycycline treatment during the IVF cycle (n = 45). In doxycycline group, doxycycline (100 mg twice daily) was started 1 week before anticipated oocyte retrieval and was continued for 1 week after oocyte retrieval. In salpingectomy group, the mesosalpinx was coagulated as close as possible to the fallopian tube.ResultsThe implantation, clinical pregnancy, ongoing pregnancy and live birth rates were significantly higher in the salpingectomy group (20.87% Vs. 9.91%, P value =0.007, 44.62% Vs. 20%, P value = 0.002, 39.62% Vs. 17.78%, P value = 0.005 and 37.31% Vs. 15.56%, P value = 0.005 respectively).ConclusionSalpingectomy is more effective than extended doxycycline treatment in improving the outcomes of IVF-ET in patients with hydrosalpinx undergoing IVF-ET. Further, larger well designed randomized controlled trials should be conducted to confirm the findings of this study.

Effects of cetrorelix versus ganirelix in gonadotropin-releasing hormone antagonist cycles for preventing premature luteinizing hormone surges and on clinical outcomes of IVF-ET cycles

To compare the effects of cetrorelix and ganirelix in gonadotropin-releasing hormone antagonist (GnRH-ant) cycles for preventing premature luteinizing hormone (LH) surges and on clinical outcomes of IVF-ET cycles. We retrospectively analyzed 2572 GnRH-ant cycles of in vitro fertilization and embryo transfer from January, 2013 to December, 2016, including 1368 cycles with cetrorelix treatment and 1204 cycles with ganirelix treatment. The baseline characteristics of the patients and the clinical outcomes of the two groups were compared. Compared with those receiving ganirelix treatment, the patients with cetrorelix treatment had a significantly younger age (33.10 vs 33.89 years, P < 0.001) and a lower body mass index (21.57 vs 21.84 kg/m2, P=0.024). After adjustment for age and body mass index of the patients, no significant differences were found between the two groups in the levels of follicle-stimulating hormone (FSH), LH, estradiol (E2), progesterone (P) levels either at the baseline or on the day of hCG triggering, or in the number of oocytes retrieved (P > 0.05). The two groups also had comparable percentages of patients with LH > 10 U/L on the day of hCG triggering (3.7% vs 3.2%) and similar spontaneous ovulation rate (0.6% vs 0.5%), clinical pregnancy rate (47.7% vs 45.9%) and live birth rate (37.5% vs 33.6%) following fresh embryo transfer (P > 0.05). The incidence of moderate to severe ovarian hyperstimulation syndrome, however, was significantly higher in ganirelix group than in cetrorelix group (0.7% vs 0.1%, P=0.006). Cetrorelix and ganirelix can achieve comparable effects for preventing premature LH surges and can achieve similar clinical outcomes of GnRH-ant cycles, but ganirelix is associated with a significantly higher incidence of moderate to severe ovarian hyperstimulation syndrome.

Intrauterine injection of human chorionic gonadotropin before embryo transfer can improve in vitro fertilization-embryo transfer outcomes: a meta-analysis of randomized controlled trials

To evaluate whether intrauterine injection of hCG before embryo transfer can improve IVF-ET outcomes. Meta-analysis. Not applicable. Infertile women who underwent IVF-ET and received an intrauterine injection of hCG before ET. Infertile women treated with or without intrauterine hCG injection before ET. The primary outcomes were live birth rate (LBR), ongoing pregnancy rate (OPR), and clinical pregnancy rate (CPR), and the secondary outcomes were implantation rate (IR) and miscarriage rate (MR). Odds ratios with 95% confidence intervals (CIs) and successful ET rates were pooled to determine the effects of hCG on IVF-ET outcomes. Fifteen randomized controlled trials (RCTs) with a total of 2,763 participants were included. Infertile women in the experimental group (treated with intrauterine hCG injection before ET) exhibited significantly higher LBR (44.89% vs. 29.76%), OPR (48.09% vs. 33.42%), CPR (47.80% vs. 32.78%), and IR (31.64% vs. 22.52%) than those in the control group (intrauterine injection of placebo or no injection). Furthermore, MR was significantly lower (12.45% vs. 18.56%) in the experimental group than in the control group. The findings of this meta-analysis indicate that intrauterine injection of hCG can improve LBR, OPR, CPR, and IR after IVF-ET cycles. In addition, different timing and dosages of hCG administration may exert different effects on IVT-ET outcomes. Notably, infertile women treated with 500 IU hCG within 15minutes before ET can achieve optimal IVF-ET outcomes.

Do poor-responder patients undergoing IVF benefit from splitting and increasing the daily gonadotropin dose?

We aim to retrospectively evaluate the role of increasing the gonadotropin daily dose from 450 IU/day to 300 IU twice a day on IVF-ET outcome in poor responder patients. All consecutive women admitted to our IVF unit and underwent COH consisting of daily gonadotropin dose of 450 IU, followed by an IVF cycle using 300 IU twice a day, were included. Ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and pregnancy rate was assessed. Twenty-three patients undergoing both cycles were evaluated. While there was no between-group difference in the duration of COH, number of 2PN embryos, fertilization rate and number of embryos transferred, patients receiving daily gonadotropin 300 IU twice a day achieved a significantly higher peak estradiol levels (3350.39 ± 2364.26 vs. 2223.74 ± 1299.91; p < .03, respectively), and yielded significantly higher number of follicles >15 mm in diameter on day of hCG administration (3.2 ± 2.4 vs 1.8 ± 1; p < .03, respectively) and higher number of oocytes retrieved (3.48 ± 2.54 vs 1.87 ± 1.1; p < .02, respectively) with an acceptable live birth rate (5%). To conclude, in poor responders undergoing COH a daily gonadotropin dose of 450 IU, increasing the dose to 300 IU twice daily may result in higher oocyte yield, with the possible improvement in IVF outcome.