Basal Serum FSH Research Articles

DIA proteomic and PRM validation through human granulose cells profiles screen suitable biomarkers for polycystic ovary syndrome patients

The aim of this study is to identify differentially expressed proteins (DEPs) in granulose cells (GCs) from women with or withoutpolycystic ovary syndrome (PCOS) via data independent acquisition (DIA) proteomic analysis.A total of 63 women were recruited for this study, 34 PCOS patients as experimental group (P), and 29 women without PCOS as Normal group (NP). DIA-based proteomic analysis was performed to identify DEPs in GCs between the P and NP samples. Certain typical DEPs were further validated by Parallel reaction monitoring (PRM), and correlation analysis was performed between these DEPs and the clinical characteristics.Cell vitality was measured by CCK-8 assay. DIA analysis revealed 174 significantly DEPs, of which 7 were upregulated and 167 downregulated. Bioinformatics analysis was performed to analysis the significantly DEPs. The PRM experiment confirmed TOP2A and SPHKAP were upregulated significantly in P by comparing to NP, while GM2A, MRPS16, APOA2 and FGF2 were downregulated significantly. Most notably, Correlation analysis revealed that TOP2A, SPHKAP, MRPS16 and FGF2were positively correlated with TG, AMH and Age, but negatively correlated with Menarche age, DBIL, FT3, Basal serum FSH and LH.Meanwhile, CCK-8 assay has shown that downregulation of FGF2 could weaken cell viability. Finally, a panel of DEPs were identified in the GCs of patients with PCOS, of which certain significant DEPs might play essential roles in the pathogenesis of PCOS, could be regarded as candidate biomarkers for PCOS.

Perinatal outcomes of singleton live births after late moderate-to-severe ovarian hyperstimulation syndrome: A propensity score-matched study.

To evaluate whether singleton live births achieved following in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in women with late moderate-to-severe ovarian hyperstimulation syndrome (OHSS) is associated with adverse perinatal outcomes. This was a single-center retrospective cohort study conducted from January 2016 to June 2021.A total of 4,012 IVF/ICSI-fresh embryo transfer cycles that achieved singleton live births were included. According to the diagnosis of OHSS, the cycles were divided into two groups: late moderate-to-severe OHSS (MS-OHSS) group (n = 114) and non-OHSS group (n = 3,898). Multiple baseline covariates were controlled by propensity score matching, yielding 114 late MS-OHSS singleton live births matched to 337 non-OHSS singleton live births. The primary outcome of the study was normal term infant. The secondary outcomes were perinatal complications, gestational age at birth, birth weight, and birth height. Before propensity score matching, no significant difference in perinatal outcomes was identified between late MS-OHSS group and non-OHSS group. After matching maternal age, BMI, basal serum FSH level, basal serum AMH level, basal antral follicle count, type of stimulation protocol, day of embryo development for embryo transfer, number of embryo transfer, and number of oocytes retrieved, there was still no significant difference in obstetric outcomes and neonatal outcomes between the two groups. The findings demonstrate that the perinatal outcomes were similar between the two groups. However, because the sample size of patients with late MS-OHSS was limited in this study, further investigations are warranted using a larger sample size.

P-325 Endometriosis has no negative effect on embryo quality and morphokinetics. A retrospective case control study

Abstract Study question Does endometriosis affect embryo quality assessed by a time-lapse morphokinetic model analysis? Summary answer Endometriosis does not seem to have a negative effect on embryo morphokinetics and embryo quality assessed by a time-lapse in-house model. What is known already Endometriosis is strongly associated with infertility. Clinical studies suggest lower implantation and pregnancy rates in women with endometriosis. Embryos of women with endometriosis exhibit a higher incidence of developmental delay and arrested development than those derived from women without the disease. Poor oocyte and embryo quality have been suggested as a possible cause. It has been found that time-lapse systems which capture images of embryos at frequent time intervals allow continuous assessment of their quality. Developing an in-house model for embryo selection based on embryos with known implantation data (KID) enables detecting the highest quality embryos selected for transfer. Study design, size, duration A retrospective case control study between July 2013 and December 2020 which evaluated embryos from 58 ICSI cycles of women with endometriosis and 487 ICIS cycles of healthy women treated for male factor infertility. Morphokinetic parameters and rate of high-quality embryos were compared. High-quality was considered as: time to pronucleus fading (tPNf)<24.08, T2<26.6, S2<0.9, and t8<56 hours following insemination for cleavage embryos, and t2<26.6, S2<0.9, t8<56 and time to start blastulation (tSB)<96.6 hours for blastocysts. Participants/materials, setting, methods At a single infertility unit, women with endometriosis were compared to healthy women with male factor infertility as the control group. The main outcome was embryo kinetics which included: time to polar body extrusion (tPB2), time to pronucleus fading (tPNf), cleavage timings (t2-t8), synchrony of the second and third cycles (S2 and S3), duration of the second cycle (CC2) time to start blastulation (tSB). These parameters were set based on an in-house morphokinetic model. Main results and the role of chance We compared 154 embryos derived from 58 ICSI cycles of women with endometriosis to 1,387 embryos derived from 487 ICSI control cycles of couples with male factor as a single cause of infertility.There was a wider use of agonist protocol (48.3% vs 15.7%,p<0.001) and a higher rate of nuliparity (81% vs 61.5%, p = 0.003) in women with endometriosis compared to the control group. Demographic and treatment parameters were comparable including: maternal age, BMI, Gravidity, number of cycles, gonadotropins dosage, basal serum FSH, basal serum LH, estradiol and progesterone level at the day of ovum pick-up, number of oocytes aspirated, number of mature oocytes. There was no difference in tPB2, tPNf, t2-t8, S2 and S3, CC2, tSB between the groups. The rate of top quality embryos was comparable for both groups; for day 3 p = 0.25 and for day 5 p = 0.72. Pregnancy rate for the study and control group was 38.8% and 45%, respectively, p = 0.36. Limitations, reasons for caution One limitation is the retrospective methodology. Endometriosis severity was not taken into account which might be a confounding factor. The strengths are a single center study with embryos cultured under the same standardized laboratory conditions. However, a larger scale study might be needed. Wider implications of the findings Time lapse in-house model is an additive informative tool for embryo quality. Opposed to what was thought so far, the use of our time-lapsed system demonstrated that embryos of women with endometriosis had similar quality to healthy women. This can be used to reassure women with endometriosis before IVF treatment. Trial registration number not applicable

Insights into ovarian response with a fixed low dose FSH stimulation in an IUI programme: the PRORAILS study.

Are patients' characteristics, such as anti-Müllerian hormone (AMH) and BMI, reliable factors to predict ovarian response in couples with unexplained subfertility undergoing IUI with ovarian hyperstimulation (IUI-OH)? We observed no solid relationship between serum AMH and ovarian response. Ovarian stimulation during IUI treatment could lead to a higher chance of pregnancy, but also a higher incidence of multiple pregnancies, unless strict cancellation criteria are being used. Several factors could influence the result of the stimulation, such as age, BMI and hormonal status of the female. In IVF treatment, AMH has shown to be a useful predictor of ovarian stimulation to optimize the outcome; however, in a milder stimulation protocol, such as IUI, this has not been investigated. We performed a prospective cohort study and evaluated the first IUI stimulation cycle of 492 patients. The study was conducted between 2012 and 2017. Follow-up ended if patients were not pregnant after the first cycle. If pregnancy did occur, follow-up lasted until delivery. PRORAILS is a large multicentre nationwide cohort study executed in the Netherlands. Eligible women aged 18-43 years who were diagnosed with unexplained subfertility or mild male subfertility according to the Dutch guideline, with a regular indication for IUI-OH, were asked to participate. Ovarian response was assessed using a transvaginal ultrasound 5-7 days after initiation of the stimulation and was repeated according to the size of the leading follicles. Ovarian response was defined as optimal or suboptimal based on the total number of dominant follicles >15 mm. A successful stimulation was defined as the presence of two to three follicles >15 mm on the day of hCG administration. Serum AMH (µg/l) was measured by ELISA, and samples were taken on day 2, 3 or 4 of the menstrual cycle. Poisson regression was used to estimate the risk of a suboptimal ovarian response. Of the 492 participants, the mean age was 33 years and the mean subfertility duration was 2.5 years. The median serum AMH was 2.1 (µg/l). The majority of patients had a suboptimal response: 326 women (66%), of whom 224 (45%) had a hypo response (defined as <two follicles sized > 15 mm) and 102 (21%) had a hyper response (defined as more than three follicles sized >15 mm). The lowest AMH category showed a trend towards a smaller risk of a suboptimal response (relative risk ratio 0.76 (95% CI 0.54, 1.06)), but this effect did not reach statistical significance. In the prediction models, BMI and serum basal FSH were significant predictors of a hypo response, while for hyper response the factors age, BMI and serum FSH were significant. A higher BMI showed a higher risk for hypo response, as did a higher FSH whereas a lower BMI and lower FSH showed a higher risk for hyper response. The addition of AMH to the models did not improve the predictive abilities. Although the study was prospective, the main analyses were cross-sectional with characteristics measured at one time-point. The study was not powered to provide insight into predictors of pregnancy and live births and, therefore, the result for pregnancy should be interpreted with caution. This was the first large multicentre study that investigated the characteristics of ovarian response categories using standardized methods and centrally analysed laboratory measures. PRORAILS is a nationwide study with 15 hospitals and, therefore, these results are generalizable to other hospitals in the Netherlands. This study provides high-quality outcomes advancing the subfertility research field. Future studies would benefit from a randomized design investigating the effectiveness of an individualized approach versus a fixed dose. Also, the relation between a good ovarian stimulation and pregnancy rate could be further investigated. The PRORAILS study is sponsored by Merck B.V., Schiphol-Rijk, the Netherlands, an affiliation of Merck KGaA, Darmstadt, Germany (EMR700623_612). Merck KGaA, Darmstadt, Germany, reviewed the manuscript prior to submission. The opinions remain those of the authors. Merck KGaA, Darmstadt, Germany, had no influence on the use of medication in this study. The recombinant FSH was mostly provided by Merck B.V. or MSD. F.B. is a member of the external advisory board for Merck B.V., Schiphol-Rijk, the Netherlands, and has received a research grant from Merck B.V., Schiphol-Rijk. H.v.B. is an employee from IQVIA, which is a commercial data-analysing company, and received payment for her part in the article. NCT01662180.

Early Cervical Lesions Affecting Ovarian Reserve and Reproductive Outcomes of Females in Assisted Reproductive Cycles.

To estimate the effects of early cervical lesions (ECL) on female reproductive function and IVF/ICSI cycle outcomes, a retrospective cohort study involving 111 infertile women from 2014 to 2019 was performed. Thirty-seven women with a history of ECL and seventy-four controls, undergoing IVF/ICSI cycles, were included in the ECL group and comparison group respectively. Demographic characteristics, ovarian reserve, and IVF/ICSI cycle outcomes of both groups were collected. Basal serum FSH level, AMH level, AFC, number of oocytes retrieved and matured, normal fertilization rate, embryo available rate, blastocyst formation rate, implantation rate, pregnancy rate, and cumulative live birth rate (CLBR) were assessed and compared. We observed that while both groups were similar concerning baseline features, significantly more women in the ECL group were diagnosed as poor ovarian response (POR), compared with those in the comparison group (27.0% vs. 10.8%, P=0.003). The pregnancy rate and LBR for a complete cycle were both significantly lower in the ECL group (38.5% vs. 58.8%, P=0.021; 28.9% vs. 48.2%, P=0.025, respectively). The conservative and optimal CLBRs for up to four complete cycles in the ECL group were also lower than those in the comparison group (40.5% vs. 55.4%, P=0.140; 45.9% vs. 67.6%, P=0.028). Longer time intervals (over one year) between ECL diagnosis/treatment and assisted reproductive technology (ART) cycle start negatively affected the pregnancy rate and LBR. In conclusion, female patients with ECL history seemingly have a lower ovarian reserve, reduced pregnancy rate, and decreased live birth rate (LBR), compared with age-matched women undergoing IVF/ICSI.

Women with polycystic ovary syndrome (PCOS) have reduced melatonin concentrations in their follicles and have mild sleep disturbances

BackgroundPolycystic ovary syndrome (PCOS) is a common gynecologic disorder related to abnormal circadian rhythm. Therefore, we aimed to find whether the level of melatonin, a rhythm regulating hormone changed in the ovarian microenvironment in this disease.MethodsThe melatonin concentrations in follicular fluid (FF) were measured in 35 PCOS and 36 non-PCOS women undergoing in vitro fertilization (IVF) treatment.ResultsThe FF melatonin concentration was significantly lower in PCOS women than non-PCOS women (p = 0.045) and it was found positively correlated with serum basal FSH level (r = 0.308, p = 0.013). In IVF procedures, there was no significant difference in the fertilization rate of oocytes between the two groups, but the high-quality embryogenesis rate on the third day of the PCOS group was significantly lower than that of the control group (p = 0.042), which showed a weak positive correlation with the FF melatonin concentration (rs = 0.240, p = 0.044). Furthermore, there was no significant difference in overall pregnancy outcome. The PSQI questionnaire showed that sleep disorders were more likely to exist in the PCOS group, though there was no significant difference.ConclusionThe obtained results suggested PCOS women had lower melatonin concentrations in the ovarian microenvironment.

Poor Ovarian Response to Gonadotrophins in PCOS Women after Laparoscopic Ovarian Drilling.

Background and Objectives: Polycystic ovary syndrome (PCOS) is a major cause of anovulatory infertility, and ovulation induction is the first-line treatment. If this fails, laparoscopic ovarian drilling (LOD) is used to induce mono-ovulations. There have been implications, that LOD can cause destruction of ovarian tissue and therefore premature ovarian failure. Furthermore, unexpected poor ovarian response (POR) to gonadotrophins can occur in PCOS women after LOD. There have been reports about FSH receptor polymorphisms found in women with PCOS that are related to higher serum FSH levels and POR to gonadotrophins. Materials and Methods: In the present study, we retrospectively analyzed data of 144 infertile PCOS women that had LOD performed before IVF. Results: Thirty of included patients (20.8%) had POR (≤3 oocytes) to ovarian stimulation with gonadotrophins. Women with POR had significantly higher median levels of basal serum FSH (7.2 (interquartile range (IQR), 6.0–9.2) compared to women with normal ovarian response (6.0 (IQR, 5.0–7.4); p = 0.006). Furthermore, women with POR used a significantly higher median cumulative dose of gonadotrophins (1875 IU (IQR, 1312.5–2400) for ovarian stimulation compared to women with normal ovarian response (1600 IU (IQR, 1200–1800); p = 0.018). Conclusion: Infertile PCOS women who experience POR after LOD have significantly higher serum FSH levels compared to women with normal ovarian response after LOD. As these levels are still within the normal range, we speculate that LOD is not the cause of POR. We presume that women with PCOS and POR after LOD could have FSH-R genotypes associated with POR and higher serum FSH levels.

Effectiveness of basal LH in monitoring central precocious puberty treatment in girls.

Treatment of central precocious puberty (CPP) is based on administration of GnRH agonists in order to suppress hypothalamic-pituitary-gonadal axis and thus induce the stabilization or regression of pubertal development. Our aim was to determine whether the single basal serum LH and/or FSH concentration could be an effective tool to assess the efficacy of treatment to suppress activation of hypothalamic-pituitary axis. Serum LH and FSH were measured before and after the GnRH injection, as well as E2 basal levels in 60 girls with documented idiopathic CPP at diagnosis and 18 and 30 months after the beginning of therapy. At diagnosis, peaks of >5IU/L of LH and of FSH were observed in 100 and 91.6% of girls, respectively, with basal LH values of <1IU/L in 70% and basal FSH levels of <1IU/L in 10%. E2 were <20pg/mL in 36.6%. After 18 months, a suppressed peak (i.e. <3IU/L) was recorded in 85% of girls (p<0.01) for LH and in 98.3% for FSH (p<0.01). Basal LH <1IU/L was detected in 85% (p<0.01) and basal FSH ≤1IU/L in 40% (p<0.01). Serum E2 ≤20pg/mL was recorded in 61.6% (p<0.01). After 30 months, all patients showed LH suppressed peak (p<0.01) and 98.3% suppressed FSH peak (p<0.01). 100% showed basal LH concentrations <1IU/L (p<0.01) and 38.3% FSH basal values <1UI/mL (p<0.01). E2 ≤20pg/mL was observed in 32.72% (p=NS). Basal LH values are a reliable indicator of the efficacy of GnRHa therapy after 30 months of GnRHa therapy.

The Relationship Between Serum Delta FSH Level and Ovarian Response in IVF/ICSI Cycles.

BackgroundWhen ovarian response to FSH stimulation for IVF/ICSI is unsatisfactory, the FSH dose is often adjusted in the treatment cycles, thereby assuming that hormone status and follicular development were insufficient for optimal stimulation.ObjectivesTo evaluate whether serum delta FSH levels between D6 of gonadotrophin use and basal serum FSH or between D6 of gonadotrophin use and D1 of gonadotrophin use predict ovarian response in IVF/ICSI cycles.MethodThe participants of this retrospective study were chosen from the Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University between August 2015 and December 2017 (n = 3,109), and during the COS, each participant was given a fixed dose of rFSH in the first 6 days. Delta FSH1: The difference of serum FSH between D6 of gonadotrophin use and basal serum FSH. Delta FSH2: The difference of serum FSH between D6 of gonadotrophin use and D1 of gonadotrophin use. Logistic regression was used to analyze the association between delta FSH1 level and delta FSH2 level and ovarian response. Besides, we also use the tertile statistics to divide the groups.ResultsPart I: Delta FSH1 levels (mean: 1.41 ± 3.46) in normal responders were higher than delta FSH1 levels (mean: 1.07 ± 23.89) in hyper responders (P = 0.0248). The tertile of delta FSH1 is dif ≤ 0, 0 < dif ≤ 2.25 and dif > 2.25. Compared with the hyper responder, the delta FSH1 (0 < dif ≤ 2.25 and dif > 2.25) in the normal responder has a higher ratio and is statistically significant. Part II: Delta FSH2 levels (mean: 4.90 ± 2.84) in normal responders were similar with delta FSH2 levels (mean: 4.74 ± 2.09) in hyper responders (P = 0.103). The tertile of delta FSH1 is dif ≤ 3.91, 3.91 < dif ≤ 5.69 and dif > 5.69. Compared with the hyper responders, the delta FSH2 (3.91 < dif ≤ 5.69 and dif > 5.69) in the normal responders has a higher ratio and is statistically significant.ConclusionsThere is a weak relationship between ovarian response and serum delta FSH levels.

Estrogens in Human Male Gonadotropin Secretion and Testicular Physiology From Infancy to Late Puberty.

Several reports in humans as well as transgenic mouse models have shown that estrogens play an important role in male reproduction and fertility. Estrogen receptor alpha (ERα) and beta (ERβ) are expressed in different male tissues including the brain. The estradiol-binding protein GPER1 also mediates estrogen action in target tissues. In human testes a minimal ERα expression during prepuberty along with a marked pubertal up-regulation in germ cells has been reported. ERβ expression was detected mostly in spermatogonia, primary spermatocytes, and immature spermatids. In Sertoli cells ERβ expression increases with age. The aromatase enzyme (cP450arom), which converts androgens to estrogens, is widely expressed in human tissues (including gonads and hypothalamus), even during fetal life, suggesting that estrogens are also involved in human fetal physiology. Moreover, cP450arom is expressed in the early postnatal testicular Leydig cells and spermatogonia. Even though the aromatase complex is required for estrogen synthesis, its biological relevance is also related to the regulation of the balance between androgens and estrogens in different tissues. Knockout mouse models of aromatase (ArKO) and estrogen receptors (ERKOα, ERKOβ, and ERKOαβ) provide an important tool to study the effects of estrogens on the male reproductive physiology including the gonadal axis. High basal serum FSH levels were reported in adult aromatase-deficient men, suggesting that estrogens are involved in the negative regulatory gonadotropin feedback. However, normal serum gonadotropin levels were observed in an aromatase-deficient boy, suggesting a maturational pattern role of estrogen in the regulation of gonadotropin secretion. Nevertheless, the role of estrogens in primate testis development and function is controversial and poorly understood. This review addresses the role of estrogens in gonadotropin secretion and testicular physiology in male humans especially during childhood and puberty.

Do young women with unexplained infertility show manifestations of decreased ovarian reserve?

To investigate whether unexplained infertility at a young age demonstrates manifestations of decreased ovarian reserve. A total of 100 women were divided into two equally sized groups. The study group comprised women aged ≤ 37years diagnosed with unexplained infertility, and the control group included age-matched women with either mechanical factor or severe male factor infertility. Both groups were comparable in their basic characteristics. Overall, women with unexplained infertility presented with inferior ovarian reserve results set against women of the control group. The number of ≥ 14-mm follicles on the day of hCG administration was significantly lower in the study compared with the control group (7.0 ± 4.5 vs. 10.4 ± 4.1 follicles, respectively, P < 0.001). Likewise, basal serum FSH was higher in the study compared with the control group (8.4 ± 5.5 vs. 6.4 ± 1.7IU/L, respectively, P = 0.015), while antral follicle count was lower (10.9 ± 6.6 vs. 16.2 ± 6.6 follicles, respectively, P < 0.001). Furthermore, women with unexplained infertility required a higher total dose of FSH for ovarian stimulation (2,923 ± 1,701 vs. 2,196 ± 941IU/L, respectively, P = 0.010), but exhibited a lower number of retrieved oocytes (9.3 ± 6.3 vs. 15.6 ± 7.9 oocytes, respectively, P < 0.001), alongside a lower number of achieved embryos (5.3 ± 4.0 vs. 8.0 ± 4.7 embryos, respectively, P = 0.002). Interestingly, the cumulative clinical pregnancy rate was not significantly different between the two groups (44% vs. 58%, respectively, P = 0.163). Young women ≤ 37years of age with unexplained infertility have clear manifestations of sub-optimal ovarian reserve set against controls. Our findings suggest that unexplained infertility at a young age may be a risk factor for developing poor ovarian response, specifically as a quantitative, rather than a qualitative, risk factor.

Predictability of consecutive measurements of serum Anti-Mullerian Hormone (AMH) during In Vitro Fertilization (IVF)

Background : In recent years, many studies had been carried out on the basal AMH level and its association with controlled ovarian hyperstimulation (COH) outcome. Only a few studies have been conducted on the correlation between COH outcomes and AMH levels measured on different stimulation days and these studies did not show a comparison between different measurement timings over the entire period of the COH cycle. Objectives: the current study aim is to assess the predictive values of basal and consecutive serum AMH levels during COH cycle. Methods and Results: One hundred women were involved in this study, scheduled for IVF program in Dwarozh Fertility Center in Sulaimanyiah , between December 2015 until January 2017, blood samples were collected for measurement of AMH, Estradiol, and FSH on day 2 of menstrual cycle, and the subsequent samples on day 4,6,8 and 10 were taking after the stimulation of ovaries with gonadotrophin. All hormones being analyzed by using electrochemiluminescence methods (Cobas 411 by Roche) as a single batch, each patient was given a unique numerical identifier, which issued in data analysis. P values &lt;0.05 were considered significant. Results: the patients' characteristics , basal serum estradiol (E2), FSH and AMH levels at day 2 of cycle and&nbsp; subsequent days after stimulation . As expected significant differences were observed for total dosage of FSH, peak E2 levels and duration of stimulation between short and long GnRH agonist groups. The ROC curve was used to assess the&nbsp; AMH values in different days (day 2, 4, 6, 8, and 10) for prediction of IVF outcomes (implantation, abortion, preganancy and live birth). All the days showed significant area under the curve (AUC) (p&lt;0.05). However, when all the ROC curve were comapred to each others there were no significance differences bwteeen them (p&gt;0.05) Conclusions: &nbsp;The present study concluded that measurement of serum AMH at any time after stimulation still predictive of the IVF outcomes which will reinforce the already known value of AMH in clinical practice.

Impact of Body Mass Index on Implantation Rate in ICSI Cycles

Background: obesity and overweight are recognized as a growing global health problem Worldwide, prevalence of overweight or obesity, defined as an adult body mass index (BMI) of 25 kg m² or greater. Patterns of overweight and obesity differ between countries, regions and by country income, with overweight or obesity more prevalent among men in developed countries and among women in developing countries. Aim of the Work: This study aimed to evaluate the impact of female increased body mass index (BMI) on implantation rate and clinical pregnancy in women undergoing ICSI cycle. Patients and Methods: this is a retrospective study conducted on a total of 400 cycles of assisted reproduction treatment has been evaluated from Orabi IVF Centre and Mit_Ghamr IVF Centre. Data recruited from patient files from January 2016 to July 2018 who did ICSI trial during this period. Patients who included in our study were sub divided into 2 groups according to BMI: 1 st group: normal weight with BMI between 18 and 24.9 kg/m2. (200 case), 2 nd group: overweight and obese women ≥ 25 kg/m2 (200 case). Results: we showed that overweight and obese infertile women had a higher basal serum FSH, LH and estradiol levels than normal weight women. In our study group the duration of infertility was progressively higher as BMI increased. The two groups were comparable regarding female age were not statistically different in both groups. The duration of infertility showed no significant difference between the two groups. As in group (1) it ranges from 10-17 years with median duration of 6 years, while in group (2) it ranges from 0.5-23 with a median duration of 5 years this result a significant difference with p-value (0.057).Conclusion: female overweight and obesity appeared to have deleterious effects on ovarian response to stimulation in women undergoing IVF and implantation rate. Moreover, female obesity compromised IVF outcome.

Impact of Body Mass Index on Implantation Rate in ICSI Cycles

Background: obesity and overweight are recognized as a growing global health problem Worldwide, prevalence of overweight or obesity, defined as an adult body mass index (BMI) of 25 kg m² or greater. Patterns of overweight and obesity differ between countries, regions and by country income, with overweight or obesity more prevalent among men in developed countries and among women in developing countries. Aim of the Work: This study aimed to evaluate the impact of female increased body mass index (BMI) on implantation rate and clinical pregnancy in women undergoing ICSI cycle. Patients and Methods: this is a retrospective study conducted on a total of 400 cycles of assisted reproduction treatment has been evaluated from Orabi IVF Centre and Mit_Ghamr IVF Centre. Data recruited from patient files from January 2016 to July 2018 who did ICSI trial during this period. Patients who included in our study were sub divided into 2 groups according to BMI: 1 st group: normal weight with BMI between 18 and 24.9 kg/m2. (200 case), 2 nd group: overweight and obese women ≥ 25 kg/m2 (200 case). Results: we showed that overweight and obese infertile women had a higher basal serum FSH, LH and estradiol levels than normal weight women. In our study group the duration of infertility was progressively higher as BMI increased. The two groups were comparable regarding female age were not statistically different in both groups. The duration of infertility showed no significant difference between the two groups. As in group (1) it ranges from 10-17 years with median duration of 6 years, while in group (2) it ranges from 0.5-23 with a median duration of 5 years this result a significant difference with p-value (0.057).Conclusion: female overweight and obesity appeared to have deleterious effects on ovarian response to stimulation in women undergoing IVF and implantation rate. Moreover, female obesity compromised IVF outcome.

Circulating 25-hydroxyvitamind concentrations among infertile couples and associations with IVF /ICSI outcome

Through examining the level of serum vitamin D in couples undergoing IVF/ICSI, the study was aimed to investigate whether serum vitamin D correlated with fertilization, embryo development and endometrial receptivity in IVF/ICSI. Between March 2016 and March 2017, we performed a large retrospective, non-interventional, single-center cohort study and measured 25OHD plasma levels prior to controlled ovarian stimulation in couples who underwent IVF/ICSI(including 3055 couples). The inclusive criteria were:1) female age between 20 and 42 years old without poor ovarian response according to Bologna criteria; 2) serum basal FSH≤10 mIU/ml. In this study, sperm or egg donation, ovum frozen, no oocyte for fertilization, chromosome abnormalities, congenital dysplasia of gonadal were excluded from this study.We excluded the couples if the time break between serum 25(OH)D measurement and ovum pick-up was over a season. Several statistical methods were employed in this study, including Pearson correlation coefficient, multiple linear regression and regression of binary logistic. The primary outcome were normal fertilization rates, top-quality embryo rates, implantation rates, clinical pregnancy rates and abortion rates. Women were grouped by serum 25OHD quartiles:≦14.8 ng/ml (Q1), 14.9-19.6 ng/ml (Q2), 19.7-24.7 ng/ml (Q3), ≧24.8 ng/ml (Q4). In women undergoing IVF, the baseline characteristics between groups were comparable and normal fertilization rates were 60.06%,62.55%,62.90% and 65.53%, respectively(P=0.003). There was a positive correlation between maternal serum 25OHD conditions and normal fertilization rates (r=0.09, P<0.001). Binary logistic regression was employed to assess whether 25(OH)D groups correlated with low fertilization rate(LFR), in which LFR was set as dependent variable and 25 (OH)D groups as independent variable. Unadjusted odds ratio(OR)was 2.78 (P=0.022) comparing patients with 25OHD in the Q1 versus Q4. After adjusting for confounders, 25OHD ≦14.8 ng/mL (Q1) was associated with 1.86 times more than levels ≧24.8 ng/mL (Q4) of suffering low fertilization rate (OR =2.86, P=0.031). The adjusted ORs for the Q2 and Q3 were indistinguishable from OR = 2.79 (P=0.035) and OR = 1.68 (P=0.318). What’s more, top-quality embryos rates, implantation rates, clinical pregnancy rate, abortion rates and vitamin D levels in women were not correlated. In men, we could not find significant differences in fertilization rates, embryo development and clinical pregnancy rates according to vitamin D status. Maternal vitamin D mainly may have an effect on fertilization process in IVF, but not on embryo development and endometrial receptivity. Besides, fertilization, embryo development and endometrial receptivity were not correlated with serum 25 OHD levels in men. Further randomized controlled trials about vitamin D supplementation and fertilization process were merited.

Antral Follicle Diameter Variance Within Each Ovary May Be A Predictor For Poor Response In Cases With Normal Ovarian Reserve.

To determine the predictive value of antral follicle diameter variance within each ovary for ovarian response in cases with normal ovarian reserve tests. This is a prospective observational study. One hundred and thirty nine infertile women who underwent ART in IVF-ICSI unit of Zeynep Kamil women and children's Health Training and research hospital between January 2017 to June 2017 were recruited. Blood samples were collected on day 2/day 3 for assessment of serum FSH and estradiol. Trans-vaginal sonography was done for antral follicle count. During antral follicle count, in order to determine antral follicle diameter variance, diameters of the largest and smallest follicles were recorded. Variance was calculated by subtracting the smallest diameter from the largest one. Following ovarian stimulation with antagonist protocol, poor response was determined in cases with total oocyte number≤3. Ovarian reserve tests and antral follicle diameter variance were utilized to predict cases with poor response in women with normal ovarian reserve. Antral follicle diameter variance both in right (AUC=0.737, P<0.001) and left (AUC=0.651, P<0.05) ovaries significantly predicted poor ovarian response. Variance>3.5 mm was found to have 75% sensitivity to predict poor response. Basal serum FSH with estradiol levels and AFC failed to predict poor response (P>0.05). Other significant predictors for poor response were day 5 estradiol level and estradiol level at trigger day (P<0.05). In multivariate regression analysis, both AFC and antral follicle diameter variance in the right ovary were found to be significantly associated with clinical pregnancy, on the other hand peak estradiol concentration and antral follicle diameter variance in the right ovary were significantly associated with poor response. Antral follicle diameter variance may be utilized to predict poor ovarian response in cases with normal ovarian reserve.

Does ovarian reserve affect outcomes in single ideal blastocyst transfers in women less than 40years of age?

There is much debate whether diminished ovarian reserve is purely a quantitative issue, or if quality as determined by pregnancy potential of the ensuing oocytes is also affected. The purpose of this study was to determine whether diminished ovarian reserve, as established by one of three ways described below, affects pregnancy outcomes of women under 40years old undergoing a single ideal blastocyst transfer. This was a retrospective cohort study, including 507 women undergoing an ideal quality single embryo transfer between August 2010 and March 2014. Logistic regression was used to control for age, duration of infertility, parity, body mass index, and smoking status. For analysis, women were stratified for: antral follicle counts (≤5 vs.>5), basal serum FSH levels (<13 vs.≥13IU/L), and quartile of total FSH dose required for stimulation. In stratifying women by antral follicle count (AFC)≤5 vs.>5, the pregnancy rate (40 vs. 53%, p=0.04), clinical pregnancy rate (29 vs. 46%, p=0.02), and live birth rate (13 vs. 43%, p=0.001) were superior with AFC>5. Using FSH levels (<13 vs.≥13IU/L), the pregnancy rate (50 vs. 31%, p=0.27), clinical pregnancy rate (40 vs. 13%, p=0.45), and live birth rate (38 vs. 13%, p=0.48) were similar. Examining quartiles of FSH stimulation, the pregnancy rates were similar (from lowest to highest: 45, 52, 54, 41%, p=0.13); however, clinical pregnancy rate (36, 43, 47, 25%, p=0.003) and live birth rate (32, 38, 44, 20%, p=0.005) were superior in lower quartiles vs. the highest quartile. Ovarian reserve may affect embryo pregnancy potential and outcomes when measured by AFC and exogenous stimulation but not by basal FSH levels.

Ovarian response to controlled ovarian hyperstimulation: what does serum FSH say?

Do serum FSH levels on day of hCG trigger differ between women with a poor, normal or hyper response to a fixed daily dose of 150 IU recombinant FSH (rFSH)? There is no consistent relationship between ovarian response and serum FSH levels on day of hCG trigger in a 150 IU fixed dose treatment protocol. When ovarian response to stimulation for IVF/ICSI is suboptimal, the FSH dose is often adjusted in a subsequent cycle, thereby assuming that serum FSH levels were inadequate for optimal stimulation. Nested cohort study within a randomized controlled trial conducted at the University Medical Centre Utrecht between March 2009 and July 2011. Blood was drawn from 124 women on cycle Day 2 and on day of hCG triggering. Serum FSH level was determined by the Beckman-Coulter Unicel DXi800 chemiluminescence assay. In order to detect a difference of 2 IU/L between poor, normal and hyper responders, a total of 64 participants (16 poor, 32 normal and 16 hyper responders) would provide 80% power, assuming a standard deviation of 2 and an alpha of 0.05. Women aged ≤39 years with a regular cycle and fixed FSH dose of 150 IU. Exclusion criteria: BMI > 32 kg/m2 and >2 previous unsuccessful IVF/ICSI cycles. The primary outcome measure was serum FSH level on day of triggering. Median [range] body weight was 70.0 kg [55.0-85.6], 68.0 kg [52.0-94] and 60.6 kg [51.0-78.0] for poor (n = 16), normal (n = 94) and hyper (n = 17) responders, respectively. Mean (SD) serum FSH levels on day of triggering were 9.5 IU/L (2.4) in poor, 10.4 IU/L (2.3) in normal and 11.5 IU/L (2.2) in hyper responders. Serum FSH levels on day of hCG in poor responders differed significantly as compared to those in hyper responders (P = 0.03). The number of retrieved oocytes is only minimally determined by serum FSH level on the day of hCG trigger. After correction for age, body weight, basal serum FSH and basal anti-Mullerian hormone the correlation between serum FSH level on the day of hCG and ovarian response regarding the number of retrieved oocytes disappeared. The current study shows that a poor response is not related to inadequate serum FSH levels per se. One could therefore question whether increasing the rFSH dose in women with a suboptimal response is meaningful. In women with a hyper response, however, lowering the dose of rFSH in a subsequent IVF cycle may lead to lower serum FSH levels and thereby mitigate ovarian response and improve safety of the IVF treatment. As this was not a dose-response study, future research should assess whether dose adjustments benefit the poor and hyper responder. No external funds were obtained for this study. S.C.O, T.C.v.T., O.H., H.L.T., E.G.W.M.L., C.B.L. and M.J.C.E. have nothing to disclose. F.J.M.B. receives monetary compensation: member of the external advisory board for Merck Serono and Ferring, the Netherlands; educational activities for Ferring BV, the Netherlands; consultancy work for Gedeon Richter, Belgium; strategic cooperation with Roche on automated AMH assay development and research cooperation with Ansh Labs.

Effect of normal sperm morphology rate (NSMR) on clinical outcomes for rescue-ICSI(R-ICSI) patients

Purpose: To investigate whether the normal sperm morphology rate (NSMR) can affect the clinical outcomes of rescue-ICSI(R-ICSI) patients. Methods: Based on different NSMR, the patients were divided into two groups as follows: NSMR < 4% and NSMR ≥ 4% group. Main outcomes compared were fertilization, cleavage, normal fertilization, high-quality embryo, transferrable embryo, no transferrable embryo cycles, implantation, clinical pregnancy and abortion rate. Some men’s and women’s basic parameters were compared between pregnancy and non-pregnancy group. Results: The basic parameter such as female age, endometrial thickness, infertility duration, Gn administration, Gn days, basal serum FSH and basal serum E2 found no significant difference between NSMR < 4% and NSMR ≥ 4% group (p > 0.05). There was no significant difference in aspects of the number of retrieved oocytes, the number of transferred embryos, fertilization, cleavage, normal fertilization, high-quality embryo, transferrable embryo, no transferred embryo cycle, implantation, clinical pregnancy and abortion rate between two groups (p > 0.05). Between pregnancy and non-pregnancy group, we observed no significant difference in the female age, the number of retrieved oocytes, the number of high-quality embryo, the number of transferrable embryos, Gn administration, Gn does, endometrial thickness, infertility duration, basal serum FSH, basal serum E2, sperm concentration and progressively motile sperm (p > 0.05). Conclusions: Teratospermia made no effect on clinical outcomes of rescue-ICSI(R-ICSI) patients.

Endometriosis may be associated with mitochondrial dysfunction in cumulus cells from subjects undergoing in vitro fertilization-intracytoplasmic sperm injection, as reflected by decreased adenosine triphosphate production

To determine whether endometriosis is associated with mitochondrial dysfunction in cumulus (granulosa [GC]) cells of subjects undergoing IVF-intracytoplasmic sperm injection (ICSI). Prospective cohort study. An IVF clinic in a tertiary academic care center. Eleven women with endometriosis and 39 controls. None. Cumulus cell adenosine triphosphate (ATP) levels, mitochondrial DNA (mtDNA), and genomic DNA (gDNA) number. Cumulus cell ATP content was 65% lower in subjects with surgically proven endometriosis (median 312.5 attomoles/ng total DNA, interquartile range = 116.0-667.8) compared with controls (median 892.4 attomoles/ng total DNA, interquartile range = 403.0-1,412.2). There was no significant difference in mtDNA:gDNA ratio. There were no significant differences in age, body mass index (BMI), basal serum FSH level, total oocyte number, metaphase II (M2) oocyte number, metaphase I oocyte number, percentage of M2 oocytes, fertilization rate, implantation rate, or pregnancy rate (PR). Multivariate regression analysis showed significant positive correlations between ATP and [1] M2 oocyte number (r = 0.307) and [2] pregnancy (r = 0.332). There were also trends toward positive correlations between ATP and [3] age (r = 0.283), [4] total number of oocytes (r = 0.271), [5] percentage of M2 oocytes (r = 0.249), and [6] implantation rate (r = 0.293). There were no statistically significant correlations between mtDNA:gDNA ratio and any demographic factors or clinical outcomes measured. Surgically confirmed endometriosis may be associated with cumulus cell mitochondrial dysfunction in subjects undergoing IVF-ICSI for infertility, as reflected by decreased ATP production.