Basal FSH Levels Research Articles

P-664 The effect of LH levels on the day of trigger on the oocyte retrieval and maturation rates in GnRH-antagonist cycles with an agonist trigger

Abstract Study question Are LH levels on day of trigger correlated with the number of oocytes retrieved and oocyte maturation rate in GnRH-antagonist cycles with an agonist trigger? Summary answer Low LH levels on the day of trigger were associated with a lower oocyte retrieval rate yet no correlation with oocyte maturation rates was found. What is known already The concept that a bolus of gonadotrophin-releasing hormone agonist (GnRHa) can replace human chorionic gonadotrophin (HCG) as a trigger of final oocyte maturation was introduced several years ago. GnRHa trigger offers important advantages including the prevention of ovarian hyperstimulation syndrome (OHSS) with the elicitation of an endogenous LH and FSH surge. Therefore, we sought to evaluate whether LH levels on the day of the trigger are associated with the efficacy of the trigger in eliciting endogenous LH surge and thereby influencing oocyte retrieval and oocyte maturation rates. Study design, size, duration This retrospective single center study included all GnRH antagonist cycles triggered with GnRHa trigger (Decapeptyl 0.2mg) performed at our IVF unit between July 2013 and December 2020. We studied the association between LH levels on the day of trigger and the number of oocytes retrieved. Additionally, we studied the effect of LH levels on oocyte maturation rates. Participants/materials, setting, methods All GnRH antagonist cycles triggered with GnRHa trigger were included. Data was acquired through individual review of medical records. Linear regression was used to study the correlation between LH levels and oocyte retrieval and maturation rates. Moreover, LH levels on day of trigger were divided ≤1 IU/L and > 1 IU/L to further investigate this correlation. The ratio between Basal LH and LH on day of trigger was investigated as well. Main results and the role of chance There were 211 GnRH antagonist cycles triggered with GnRH agonist trigger during the study period. The mean age of patients in the study group was 30.1±4.8 y/o, mean basal LH levels were - 6.8±3.4 IU/L, mean Basal FSH levels were - 6.7±1.9IU/L and the mean total dose of gonadotropin administered was 1633.4±680.6 Units. The mean E2 levels were 11,444±7018.5 pmol/L and the mean number of oocytes retrieved was 19.8±10.2. A correlation was found between lower LH levels on the day of trigger and the number of oocytes retrieved (p < 0.001). No correlation was found between LH levels on the day of trigger and oocyte maturation rates (p = 0.82). The ratio between Basal LH and LH on day of trigger was not found to be a significant factor influencing either the number of oocytes retrieved or oocyte maturation rate. When dividing the group by LH on day of trigger to below and above 1, a borderline difference was found relating to oocyte retrieval rate between the two groups (p = 0.06). Limitations, reasons for caution The retrospective nature of the study is the main limitation. Patients receiving GnRHa trigger are mainly a selective population of either high responders or patients for fertility preservation stimulated to retrieve many oocytes, therefore findings may not be applicable to normal or poor responders. Wider implications of the findings Low LH levels on day of trigger were found associated with lower oocyte retrieval rates. GnRHa has become an alternative to standard hCG triggering in certain situations. These are preliminary findings of an ongoing study designed to investigate the efficacy of GnRHa trigger according to cycle parameters including LH levels. Trial registration number not applicable

Assessment of Ovarian Reserve in Patients with Migraine

Objective The aim of our study is to investigate the relationship between migraine and ovarian reserve. Methods The study group consists of women between the ages of 25-51, including 44 patients diagnosed with migraine and 43 controls. Ovarian reserves were performed by antral follicle count and measured anti-Müllerian hormone level. The cohort was divided into four subgroups according to age as follows: 30 years and below, 31-35 years, 36-40 years, and 41 years of age and above. Results Of the 87 individuals included in this study, 44 were migraine patients, and 43 were healthy controls. The mean ages of the study and control groups were 34.3 (minimum: 25, maximum: 51) and 36.5 (minimum: 27, maximum: 51) years, respectively. There was no statistically significant difference between the two groups regarding age (p=0.48). In the study and control groups, respectively; mean AMH levels were 2.67 ± 2.46 ng/mL and 2.55 ± 2.38 ng/mL (p=0.819), mean basal FSH levels were 7.92 ± 2.52 U/L and 9.11 ± 3.19 U/L (p=0.066), mean basal LH levels were 6.35 ± 3.59 U/L and 6.06 ± 2.86U/L (p=0.681), mean basal estradiol levels were 65.02 ± 69.54 ng/L and 49.47 ± 27.08 ng/L (p=0.244), and mean AFC were 10.9 ± 3.9 and 10.2 ± 3.7 (p=0.435). Between subgroups aged ≤30 years, serum anti-Müllerian hormone levels were found to be significantly different (p=0.036). There was no statistically significant difference between any age subgroups in terms of antral follicle count. Conclusion In conclusion, detecting possible reduction of ovarian reserves in reproductive-age (especially younger than 30 years) migraine patients by utilizing anti-Müllerian hormone and ultrasonographic markers would allow these women to make cognizant decisions regarding marriage and family planning, as well as inform them whether they are in early menopause risk

The safety of neoadjuvant hormonal treatment in infants with cryptorchidism

The standard treatment for boys with non-syndromic cryptorchidism is an early orchidopexy. It is unclear if surgical intervention alone is enough for future fertility. Recent studies show benefit of neoadjuvant or adjuvant hormonal treatment with gonadorelin (GnRH) for spermatogonia maturation based on testicular biopsy. The aim of this prospective study was to assess the safety of this treatment in infants with undescended testis at the recommended timing of early gonadorelin administration and timing of orchidopexy. Unilateral cryptorchid full term boys were initially examined (including hormonal, physical and ultrasound examination) at the age of 2.5-3.5 months. At 6 months of age, cryptorchidism was confirmed. Those with non-syndromic cryptorchidism and palpable or sonographically detected testis were randomly assigned into two groups: with and without intranasal gonadorelin treatment. Inclusion criteria were met by 36 boys (21 in GNRH and 15 in the control groups). The following orchidopexy was performed before 12 months of age with repeated examination at time of surgery. Penile size and testicular volume (using ultrasound) and basal serum levels of LH, FSH, testosterone, Inhibin B and AMH were recorded at age of 3.0 (mean) months and 11.0 (mean) months (date of surgery). The stimulation hormonal levels were checked during GnRH administration. Between minipuberty (mean 3 months) and time of orchidopexy (mean 11 months of age) the penile size increased significantly and similarly in both groups. There was no significant difference in the change of the volume of descended testis between the groups nor of the volume of undescended testis. In addition, we did not find any significant difference in the change (drop) of hormonal levels of LH, FSH, Testosterone, Inhibin B and AMH (Table 1a) CONCLUSION: The neoadjuvant gonadorelin stimulation in infants with unilateral undescended testis has not shown any specific effect on the development of penile size, testicular volume and hormonal levels at time of orchidopexy in comparison with boys without stimulation, and in the mid-term, this treatment can be considered safe. Further follow-up is necessary to evaluate the long-term effect of this early treatment.

Tanshinone IIA enhances the ovarian reserve and attenuates ovarian oxidative stress in aged mice.

BackgroundTanshinone IIA (TSA), a major lipophilic component extracted from the roots of Salvia miltiorrhiza Bunge, has been widely used in China for its various biological activities. However, its effect on ovarian reserve in aged mice was not studied elsewhere.ObjectivesThis study aimed to explore the effect of TSA on the ovarian reserve of aged mice as well as young mice. Forty weeks old mice (N = 40) were considered as aged group compared to 4 weeks old mice (N = 40), and these groups were subdivided into four subgroups (N = 10) to receive different doses of TSA (0, 10, 20, and 40 μg/g/day).MethodsThe effect of TSA was evaluated by counting follicular number by histological examination. Basal serum levels of FSH, LH, E2, and anti‐Mullerian hormone (AMH) were measured by ELISA. Moreover, the expression levels of antioxidant genes (CAT, Nrf2, GPX1), gap junction (Cx37), ERK1/2, and Smad5 family gene were examined at both mRNA (qPCR) and protein levels (western blot).ResultsFollicular number, level of AMH and E2, and the expression of CAT, Nrf2, and GPX1 genes increased significantly (p < 0.05) in aged mice administrated with medium (20 μg/g/day) and high (40 μg/g/day) doses of TSA, whereas FSH and LH levels were significantly low compared to low dose (10 μg/g/day) and control (0 μg/g/day) aged subgroups. However, we did not observe any effect of all doses of TSA on young mice.ConclusionsAdministration of TSA with medium and high doses up‐regulates the expression of antioxidative genes, reduces the oxidative injury, increases levels of AMH, and E2 levels that are relatively comparable to those in young mice, and consequently results in a healthy oocyte development.

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.

Effect of Genetic Variants of Gonadotropins and Their Receptors on Ovarian Stimulation Outcomes: A Delphi Consensus.

BackgroundA Delphi consensus was conducted to evaluate the influence of single nucleotide polymorphisms (SNPs) in genes encoding gonadotropin and gonadotropin receptors on clinical ovarian stimulation outcomes following assisted reproductive technology (ART) treatment.MethodsNine experts plus two Scientific Coordinators discussed and amended statements plus supporting references proposed by the Scientific Coordinators. The statements were distributed via an online survey to 36 experts, who voted on their level of agreement or disagreement with each statement. Consensus was reached if the proportion of participants agreeing or disagreeing with a statement was >66%.ResultsEleven statements were developed, of which two statements were merged. Overall, eight statements achieved consensus and two statements did not achieve consensus. The statements reaching consensus are summarized here. (1) SNP in the follicle stimulating hormone receptor (FSHR), rs6166 (c.2039A>G, p.Asn680Ser) (N=5 statements): Ser/Ser carriers have higher basal FSH levels than Asn/Asn carriers. Ser/Ser carriers require higher amounts of gonadotropin during ovarian stimulation than Asn/Asn carriers. Ser/Ser carriers produce fewer oocytes during ovarian stimulation than Asn/Asn or Asn/Ser carriers. There is mixed evidence supporting an association between this variant and ovarian hyperstimulation syndrome. (2) SNP of FSHR, rs6165 (c.919G>A, p.Thr307Ala) (N=1 statement): Few studies suggest Thr/Thr carriers require a shorter duration of gonadotropin stimulation than Thr/Ala or Ala/Ala carriers. (3) SNP of FSHR, rs1394205 (−29G>A) (N=1 statement): Limited data in specific ethnic groups suggest that A/A allele carriers may require higher amounts of gonadotropin during ovarian stimulation and produce fewer oocytes than G/G carriers. (4) SNP of FSH β-chain (FSHB), rs10835638 (−211G>T) (N=1 statement): There is contradictory evidence supporting an association between this variant and basal FSH levels or oocyte number. (5) SNPs of luteinizing hormone β-chain (LHB) and LH/choriogonadotropin receptor (LHCGR) genes (N=1 statement): these may influence ovarian stimulation outcomes and could represent potential future targets for pharmacogenomic research in ART, although data are still very limited.ConclusionsThis Delphi consensus provides clinical perspectives from a diverse international group of experts. The consensus supports a link between some variants in gonadotropin/gonadotropin receptor genes and ovarian stimulation outcomes; however, further research is needed to clarify these findings.

VEGF Concentration in a Preovulatory Leading Follicle Relates to Ovarian Reserve and Oocyte Maturation during Ovarian Stimulation with GnRH Antagonist Protocol in In Vitro Fertilization Cycle.

Serum vascular endothelial growth factor (VEGF) is involved in follicular vascularization, oxygenation, and consequently in oocyte maturation and embryo development. Unanswered questions remain regarding the relationship of intrafollicular VEGF level in preovulatory leading follicles to oocyte maturation and ovarian reserve during ovarian stimulation. We conducted this study to investigate the relationship of intrafollicular VEGF level in the fluid of single preovulatory leading follicles to ovarian reserve and oocyte maturation in patients receiving GnRH antagonist in vitro fertilization (IVF) protocol treatment. One hundred and eighty-five patients receiving IVF treatment were recruited and assigned to low-, normal-, and high-ovarian-reserve groups according to their serum anti-Müllerian hormone (AMH) level. Follicular fluid (FF) in preovulatory leading follicles, serum profiles, and clinical variables were collected for analysis. The result disclosed a significant among-group difference in FF VEGF concentration. Moreover, the serum AMH level was also negatively correlated with FF VEGF level. The oocyte maturation rate tended to be increased at higher AMH levels. FF VEGF concentration was significantly positively correlated with basal FSH level. In conclusion, FF VEGF concentration has a negative association with ovarian reserve level and oocyte maturation rate in patients undergoing GnRH antagonist IVF protocols.

ENDOMETRIOSIS ASSOCIATED WITH A LOWERED CUMULATIVE LIVE BIRTH RATE IN IVF BY COMPROMISING THE QUANTITY AND QUALITY OF EMBRYOS

What is the impact of endometriosis on the cumulative live birth rate (CLBR) among the patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment by using fresh plus linked frozen embryo transfer cycles with first conventional stimulation? A retrospective cohort study was carried out by recruiting a total of 3071 patients undergoing IVF/ICSI treatment at the Reproductive Medicine Center of Shenzhen Zhongshan Urology Hospital between January 2012 and December 2014. 436 patients diagnosed as endometriosis by imageological and/or surgical approaches were assigned into the study group to compare with the 2635 subjects with tubal factor infertility in the control group throughout the IVF/ICSI treatment. Measurements for primary outcomes included cumulative live birth rate per initiated cycle, while secondary outcomes were evaluated by the number of retrieved oocytes , metaphase II oocytes, transplantable embryos, good embryos, clinical pregnancy rate, and live birth rate independent in fresh and cryopreserved cycles. Bivariate followed by multivariate logistic regression analysis was conducted, with the differences analyzed by Chi squared test and Student’s t-test as appropriate. The two groups are comparable in clinical pregnancy rate and miscarriages rate in both of the fresh (56.64% vs. 57.03%, p=0.903) (9.49% vs. 13.58%, p=0.153) and the frozen-thawed embryo transfer cycles (47.6% vs. 54.3%, p=0.062) (22.4% vs. 15.3%, p=0.068). However, the live birth rate, though about the same level in the two groups in fresh embryo transfer cycles (47.47% vs. 46.20%, p=0.673), was significantly lower in the endometriosis group in frozen embryo transfer cycles (33.78% vs. 43.74%, p=0.005), thus leading to a declined CLBR with statistical significance (51.83% vs. 60.87%, p < 0.001). The results of Logistic regression analysis also revealed a lower CLBR of the patients with endometriosis. Given that the inter-group differences were present in multiple aspects such as age, AFC, as well as the basal FSH and BMI levels, multivariate Poisson regression was performed aiming to remove the confounders through adjusting these baseline factors, with a result indicating a close association between endometriosis and low CLBR (OR=1.525; 95%CI, 1.123-2.070; p = 0.007). The results from our study suggest that endometriosis is very likely to be associated with a lowered CLBR in IVF by compromising the quantity and quality of embryos, which seems to be more evident in young women with endometriosis. So young infertility patients with endometriosis should actively start ART treatment as soon as possible.

How Can the Maternal Age and the Basal Level of Serum FSH Predict the ICSI Outcome?

How Can the Maternal Age and the Basal Level of Serum FSH Predict the ICSI Outcome?

P–705 Basal FSH and AMH profiles impact embryo morphokinetics in a maternal age-dependent manner

Abstract Study question Do maternal AMH and basal FSH profiles impact embryo morphokinetics and does this relationship change with maternal age? Summary answer Embryo morphokinetics varies with basal FSH and AMH levels and this relationship changes in advanced maternal age (AMA). What is known already Basal FSH and AMH levels have been utilised as markers of ovarian reserve/response and IVF/ICSI outcomes. Basal FSH better reflects post-IVF/ICSI live birth occurrence in pre-AMA patients, while AMH appears more robust in AMA patients. Whilst plasma AMH levels reflect oocyte yield, recent data suggest that plasma basal FSH and intrafollicular AMH levels specifically reflect oocyte quality. Oocyte and embryo developmental competence is associated with faster fertilisation and embryonic morphokinetics. The assessment of the relationship between developmental morphokinetics and maternal basal FSH and AMH plasma profiles shall contribute for a better understanding of their roles as fertility markers and regulators. Study design, size, duration Retrospective cohort study including 1961 first autologous ICSI cycles performed from 2014 to 2020, providing 10774 embryos grouped according to maternal AMH and basal FSH levels in: CF [concordant favourable; AMH&amp;gt;1 (ng/mL), FSH≤10 (IU/L); n = 8055)]; DFA (discordant with favourable AMH; AMH&amp;gt;1, FSH&amp;gt;10; n = 768); DFF (discordant with favourable FSH; AMH≤1, FSH≤10; n = 1362) and CU (concordant unfavourable; AMH≤1, FSH&amp;gt;10; n = 589). Morphokinetic parameters were compared among groups in total, ≤35 (pre-AMA) and &amp;gt;35 (AMA) years old patients, separately. Participants/materials, setting, methods Patients aged 20 to 45 with FSH and AMH levels measured on menstrual cycle day 2 underwent ovarian stimulation, ovum pick-up and ICSI. Embryos were cultured in a time-lapse incubator (Embryoscope). Fertilisation and cleavage morphokinetic parameters [tPNa (time of pronuclei appearance, tPNf (time of pronuclei fading), t2, t3, t4, t5 and t8] were annotated and compared among AMH/FSH groups with the Kruskal-Wallis nonparametric test, followed by a post hoc multiple comparison with Bonferroni correction. Main results and the role of chance In overall embryos, tPNa, tPNf, t2 and t3 varied between AMH/FSH groups. CF were faster than CU embryos for all these parameters [(mean±SEM; hours); tPNa: 6.8±0.02 vs. 7.1±0.08; tPNf: 24.13±0.04 vs. 24.49±0.14; t2: 27.05±0.05 vs. 27.36±0.16; t3: 36.94±0.07 vs. 37.54±0.22 (p &amp;lt; 0.001)]. In addition, CF were faster than DFA (p &amp;lt; 0.001), but not than DFF embryos, for tPNf (CF: 24.13±0.04; DFF: 24.23±0.14; DFA: 24.57±0.14) and t2 (CF: 27.05±0.05; DFF: 27.22±0.12, DFA: 27.42±0.15). In AMA patients, faster morphokinetics was observed when one or both hormonal values were favourable; tPNf, t2 and t3 were reached earlier in CF compared to CU (tPNf: 24.17±0.05 vs. 24.52±0.15; t2: 27.13±0.06 vs. 27.43±0.17; t3: 37.09±0.08 vs. 37.63±0.24; p &amp;lt; 0.05), but not to DFF (tPNf: 24.22±0.12; t2: 27.27±0.14, t3: 36.92±0.19) or DFA embryos (tPNf: 24.39±0.14; t2: 27.34±0.17, t3: 37.26±0.23). Differently, in pre-AMA patients, faster morphokinetics was associated with favourable basal FSH regardless of AMH levels; tPNa and tPNf were reached earlier in CF compared to DFA and CU (p &amp;lt; 0.005), but not to DFF embryos (tPNA: 6.68±0.03, 6.96±0.13, 7.13±0.14, 7.12±0.19; tPNf: 24.05±0.07, 24.27±0.21, 25.14±0.34, 24.37±0.36; for CF, DFF, DFA and CU, respectively). Limitations, reasons for caution Our study is subjected to the intrinsic limitations of a retrospective analysis and the results could have been affected by variables that were not controlled for. Wider implications of the findings: The findings suggest that lower basal FSH levels are associated with faster early morphokinetics likely reflecting superior oocyte quality in pre-AMA patients. The present data may contribute to improve ART prognostic strategies and provide valuable clues for a better understanding of hormonal regulation of oocyte developmental competence. Trial registration number Not applicable

P–368 Dynamic metabolomic profiling during early implantation period

Abstract Study question To investigate the different metabolomic profiling in serum between pregnant and non-pregnant women during early implantation period. Summary answer Metabolomics of progesterone-related hormones enhances from ET day3 for pregnancy women compared with non-pregnancy women. What is known already Metabolomics is based on high-throughput analytical methods to identify and quantify metabolites. Compared to other omics study, metabolomics is the closest one to the phenotype, allowing the observation of dynamic changes in phenotype at specific timepoints. So far there is no published work about the metabolomics profile in human early implantation period. Study design, size, duration: Study design: comparative study. Size: 14 pregnancy women and 14 non-pregnancy women. duration: time-course. Participants/materials, setting, methods Participants: pregnancy women and unpregnancy women after embryo transfer (ET). Setting: university-based study. Methods: Peripheral blood were collected at ET day0, 3, 6 and 9. metabolomic profiling in serum by platforms of capillary electrophoresis-mass spectrometry (CE-MS) and liquid chromatography–mass spectrometry (LC-MS). Main results and the role of chance There were no statistical difference of the age, BMI, basal FSH level, endometrium thickness on the day of embryo transfer, distribution of primary and secondary fertility, embryo transfer cycle as well as the infertile types between the two groups. After deleting those with over 50% missing data, we finally have 310 metabolites into statistical analysis. Among the 310 metabolite, lipid metabolites account the largest percentage, nearly half of all metabolites. The second biggest class of metabolites in our data was organic acids. Combined results in repeated measurement ANOVA (RM-ANOVA) and ANOVA-simultaneous component analysis (ASCA) as well as multivariate empirical Bayes time-series analysis (MEBA), we finally found that progesterone-related hormones were the most important metabolites for the whole time-series data. Those significant metabolites showed a significant down regulation from ET day0 to ET day3 and up regulation from ET day3 to ET day9. Limitations, reasons for caution we have limited sample size for this study and further validation is necessary for confirmation. Wider implications of the findings: The phenomenon of upregulation of progesterone-related hormones from day3 in pregnancy group might be related to the embryo-originated hcg. Because the embryo has entered into endometrium at day3 and produced cytokines, hcg and other interaction with endometrium. Trial registration number NA

P–673 A visualized clinical model predicting cumulative pregnancy rate after IVF-ET: a real-world study

Abstract Study question How is the cumulative pregnancy probability of individual patients after IVF-ET,could we develop a visualized clinical model to predict it based on patient’s characteristics? Summary answer The visualized clinical mode incorporates five items of female age, number of oocytes, antral follicle count, endometrium thickness and basal FSH level. What is known already Many factors can result in infertility, prognosis prediction is clinically relevant for making the right therapeutic strategy while avoiding overtreatment. It is also helpful in counselling, making the patient aware of possible treatment duration and estimated expense and managing patient’s expectation. Visualized clinical mode and accurate prediction would also be helpful in designing clinical trials to evaluate new treatments. Study design, size, duration We conducted a retrospective analysis of a single-center database using prospectively collected data from women who underwent IVF/ICSI treatment from January 2013 to December 2015, All the participants were followed up for at least 2 years, 3538 IVF-ET cycles were included in the study.A total of 3538 IVF/ICSI cycles were included in the study. Participants/materials, setting, methods Data from a total of 2312 IVF/ICSI cycles from January 2013 to December 2014 were randomly split into training dataset (1550, 67%) and internal validation dataset (762, 33%). A total of 1226 IVF/ICSI cycles in 2015 was applied to external validation dataset (temporal validation) Main results and the role of chance Multivariable logistic regression model combined with restricted cubic splines function was used to test independent prognostic factors and estimate their effects on treatment outcome for patients treated with IVF/ICSI. Female age, number of oocytes retrieved, AFC, endometrium thickness and basal FSH were included the final model. The above model was used to calculate prediction scores for all women in the training and validation datasets. The C-index was 0.693 (95% CI: 0.692∼0.695) in training sets, 0.689 in internal validation sets and 0.710 in external validation sets, which denotes a good performance. Calibration curves suggest excellent model calibration, with an ideal agreement between the prediction and actual observation . The DCA showed that if the threshold probability is between 0 and 0.7, using the nomogram derived in the present study to predict cumulative pregnancy provided a greater benefit than either thetreat-all or the treat-none strategy. Limitations, reasons for caution it was a retrospective, single-center study.In the future, prospective, randomized controlled, multicenter clinical studies will be designed. Wider implications of the findings: The visualized nomogram model provides great predictive value for infertility patients in their first IVF/ICSI cycle, and predicts the pregnancy probability of individuals ,and could help clinicians improving clinical counselling. Trial registration number Not applicable

P–152 Morphokinetic and maternal profiles of embryos derived from centrally granulated oocytes vary with their ability to implant

Abstract Study question Does oocyte central granularity (CG) impact embryo morphokinetics and does this change with embryo implantation ability and maternal profile? Summary answer Oocyte CG slows fertilization and cleavage morphokinetics in overall derived embryos, but not in those capable to implant, an ability associated with lower maternal age. What is known already Oocyte morphology is easily accessible after pre-ICSI oocyte denudation, but the implications of morphological alterations for oocyte developmental competence are not entirely known. The presence of a centrally located granular area in the ooplasm was previously associated with alterations in the actin cytoskeleton and meiotic spindle, both potentially affecting meiosis completion, fertilization dynamics and embryo mitotic divisions. In fact, we have recently reported lower fertilization rates and delayed pronuclei fading and first cleavage associated with the presence of CG in oocytes subjected to ICSI. Study design, size, duration Retrospective analysis including 1378 control ICSI cycles providing only morphologically normal oocytes (1225 patients) and 220 CG cycles (201 patients) providing normal and CG oocytes, from July 2014 to March 2020. Morphokinetic parameters were compared between embryos from control and CG oocytes, as well as among embryos from control oocytes reaching implantation (C-I) and embryos from CG oocytes achieving (CG-I) or not (CG-NI) implantation. Maternal profiles were compared between CG-I and CG-NI. Participants/materials, setting, methods Oocytes were recovered from patients after controlled ovarian stimulation and ovum pick-up. Following ICSI, embryo culture was performed in a time-lapse incubator with annotation of time of pronuclei fading (tPNf) and cleavage times t2, t3, t4, t5 and t8. Morphokinetic data were retrospectively coupled with implantation outcomes of single transfers and of double transfers achieving double or no implantation. Differences were assessed with Chi-square and Kruskal Wallis tests. Main results and the role of chance Patients providing CG oocytes (n = 201) presented higher maternal age (37.4 ± 4.4 vs. 36.7 ± 4.3; p = 0.005), higher basal FSH (8.52 ± 3.7 vs. 7.62 ± 2.8 IU/L; p = 0.002) and lower AMH levels (2.2 ± 2.2 vs. 2.9 ± 3.1 ng/mL; p &amp;lt; 0.001) compared to control patients (n = 1225). Morphokinetic parameters from tPNf to t4 were faster in embryos derived from oocytes with normal morphology (control; n = 6947) compared to embryos derived from CG oocytes (n = 382; tPNf: 24.0 ± 3.8 vs. 24.6 ± 3.6; t2: 27.0 ± 4.3 vs. 27.6 ± 4.1; t3: 37.0 ± 5.7 vs. 37.4 ± 5.7; t4: 39.4 ± 6.4 vs. 40.1 ± 6.2 hours; p &amp;lt; 0.05). In addition, CG-NI (n = 103) embryos were slower than CG-I (n = 13) and C-I (n = 226) embryos for tPNf, t2, t3, t4 and t8 (p &amp;lt; 0.05), while CG-I did not differ from C-I embryos (p &amp;gt; 0.05; tPNf: 22.4 ± 2.6 vs. 22.0 ± 2.5; t2: 24.9 ± 2.7 vs. 24.6 ± 2.8; t3: 36.0 ± 3.5 vs. 35.4 ± 3.0; t4: 36.7 ± 3.5 vs. 36.7 ± 3.6 hours, for C-I and CG-I, respectively). Finally, patients providing CG-I embryos (n = 10) were younger than those providing CG-NI embryos (n = 65; 31.3 ± 4.6 vs. 38.0 ± 3.9; p &amp;lt; 0.05). Limitations, reasons for caution Our study is subjected to the intrinsic limitations of a retrospective analysis, the results presented could have been affected by variables that are uncontrolled for. Other studies are necessary to assess the impact of CG on clinical outcomes. Wider implications of the findings: The findings indicate that early developmental morphokinetics and maternal age constitute valid parameters for the decision of whether to transfer CG-derived embryos, as well as for the transfer prognosis. Trial registration number Not applicable

Clinical effect of adding hMG to the follicular phase long protocol for standard group with normal ovarian reserve function

Objective: To investigate the impact of adding human menopausal gonadotropin (hMG) for in vitro fertilization-embryo transfer pregnancy outcomes in a standard population of non-advanced age with normal ovarian reserve function using a long follicular phase protocol. Methods: Clinical data of 489 patients with normal ovarian reserve function, who were admitted from January 2018 to January 2020 in the Affiliated Hospital of Guizhou Medical University and underwent in vitro fertilization for the first time with the long follicular phase protocol in fresh cycles, were retrospectively analyzed. The patients were divided into three groups according to whether or not to add urine-derived hMG and the timing of addition: non-addition group (group A), medium-term hMG group (group B1), whole course hMG group (group B2); the laboratory parameters of each group were observed, and the effect of ovulation induction drugs and pregnancy outcomes were compared. Results: The ages of B1 and B2 groups were significantly higher than that of group A (P=0.019 and P=0.011). The basal FSH level of group B2 was significantly higher than those of group A and group B1 (P<0.01 and P=0.006), and the basal FSH/LH ratio of group B2 was significantly higher than that of group B1 (P=0.009). Antral follicle counts of group A and group B1 were significantly higher than that of group B2 (P=0.007 and P=0.017). The superior embryo rate of group B2 [(47±27)%] was significantly higher than that of group A (P=0.017). The embryo implantation rate of group B1 was significantly lower than those of group A and group B2 (P=0.043 and P<0.01). The clinical pregnancy rate of group B2 [76.7% (155/202)] was significantly higher than those of group A (P=0.039) and group B1 (P<0.01). The live-birth rate of group B2 [67.3% (136/202)] was significantly higher than those of group A (P=0.017) and group B1 (P=0.001). Conclusions: For non-advanced aged patients with normal ovarian reserve function, the long protocol of follicular phase is suitable for those with relatively low ovarian reserve function. Adding hMG in the whole course of ovulation induction after gonadotropin-releasing hormone agonist reduction could improve the pregnancy outcomes by improving the quality of embryos.

Female central hypogonadism with or without organic pituitary lesions: diagnostic value of LH and FSH basal levels

Female central hypogonadism with or without organic pituitary lesions: diagnostic value of LH and FSH basal levels

Thyrotropin-Secreting Pituitary Adenoma Successfully Treated With Cabergoline

Background: Thyrotropin secreting pituitary adenomas (TSH-oma) account for less than 1% of pituitary adenomas and are a rare cause of hyperthyroidism. In this case, we describe the safe use of cabergoline with the subsequent achievement of euthyroid levels and the resolution of symptoms. Clinical Case: A 67-year-old female with a presumed history of hypothyroidism for the last 3 years managed with Armour thyroid was referred for fatigue associated with palpitations, intermittent diarrhea, insomnia, and anxiety. Her TSH was noted to be suppressed at that time, and her Amour thyroid was changed to Levothyroxine 25 mcg daily, which was eventually stopped as her symptoms persisted. Follow-up thyroid function tests (TFTs) showed elevated TSH (8.60 µU/mL, reference range 0.340 - 5.600 µU/mL), and elevated free T3 (10.8 pg/mL, reference range 2.7-4.7 pg/mL) and free T4 (2.0 ng/dL, reference range 0.8-1.5 ng/dL) levels. Further laboratory workup including basal prolactin, LH, FSH, hCG α-subunit, IGF-1, and ACTH levels were within the normal range. Physical examination showed diffuse thyroid enlargement. An I-123 thyroid uptake and scan showed uniform uptake throughout the gland with no focal hyperintense areas. A dedicated pituitary MRI was performed and revealed an 8 mm microadenoma in the posterior left adenohypophysis. The patient wanted to avoid any invasive treatment and refused trans-sphenoidal surgery and medical therapy was chosen. Unfortunately, using a somatostatin analog as part of the standard medical treatment was not an option due to the high cost and lack of insurance coverage. For these reasons, a trial of cabergoline was started to suppress TSH secretion. Atenolol 25 mg daily was added temporarily for the management of her sympathetic symptoms. On periodic follow-up, her symptoms gradually subsided, and TFTs remained within normal limits. Treatment was continued for one year. Conclusion: Clinical manifestations of hyperthyroidism with biochemical evidence of elevated thyroid hormone levels and TSH levels should raise a strong suspicion for central or secondary hyperthyroidism due to TSH secreting pituitary adenoma. Cabergoline might represent an effective alternative form of medical treatment for TSH-oma in certain situations where the first line therapeutic options are refractory, contraindicated, or declined.

IVF Outcomes of Microdose Flare-up, GnRH Antagonist, and Long Protocols in Patients having a Poor Ovarian Response in the First Treatment Cycle.

To compare the IVF outcome of patients assumed to be poor responders before their first cycle treated by microdose flare-up or GnRH antagonist protocols with patients who had a poor ovarian response after their first cycle stimulated with long GnRH protocol. Observational cohort study. Department of Obstetrics and Gynecology, IVF Unit of Gazi University Faculty of Medicine, from September 2014 to February 2019. Patients treated with the first cycle of IVF and diagnosed as poor responders after ovarian stimulation were evaluated according to the treatment protocol, including microdose flare-up (Group 1: 136 patients), GnRH antagonist (Group 2: 105 patients), and long GnRH agonist (Group 3: 77 patients). Basal FSH level was significantly lower in group 3 compared to other groups (p<0.05). The number of oocytes retrieved, the number of metaphase II oocytes were similar between groups, although the mean AFC was significantly higher in group 3 than in group1 and 2 (p<0.05). Clinical pregnancy rates per patient were higher in group 3 (20.8%) than in group 1 (12.5%) and group 2 (13.3%), but the difference was not statistically significant (p=0.230). The live birth rate per patient was statistically higher in group 3 (19.5%) as compared to other groups (8.8%, 9.5%, respectively; p<0.05). Long protocol may be an option in poor responders undergoing IVF. Ovarian reserve markers are essential factors with stimulation protocol for the success of IVF in poor responder patients. Key Words: Infertility, Ovulation ınduction, Ovarian reserve, Fertilisation in-vitro, Oocyte retrieval, Pregnancy outcome, Reproductive techniques, Assisted.

Effect of unplanned spontaneous follicular growth and ovulation on pregnancy outcomes in planned artificial frozen embryo transfer cycles: a propensity score matching study.

Does unplanned spontaneous follicular growth and ovulation affect clinical outcomes after planned artificial frozen-thawed embryo transfer (AC-FET) cycles? AC-FET and spontaneous follicular growth and ovulation events resulted in notably better pregnancy outcomes with a significantly higher implantation rate (IR), clinical pregnancy rate (CPR), ongoing pregnancy rate (OPR) and live birth rate (LBR) and a significantly lower miscarriage rate. The AC-FET protocol without GnRH agonist administration is associated with a low incidence of follicular growth and ovulation. In the literature, authors often refer to these types of cycles with concern due to possibly impaired FET outcomes. However, the real impact of such cycles has yet to be elucidated due to the lack of existing data. This was a retrospective clinical study involving 2256 AC-FET cycles conducted between January 2017 and August 2019. Propensity score (PS) matching was used to control for confounding variables. Subjects were divided into two groups: a study group: cycles with spontaneous follicular growth and ovulation (the maximum diameter of follicles in any ovary was ≥14mm and ovulation was confirmed by consecutive ultrasound examinations) and a control group featuring cycles without growing follicles (the maximum diameter of follicles in both ovaries were <10mm). The study group was matched by PS with the control group at a ratio of 1:2. The study group consisted of 195 patients before PS matching and 176 patients after matching. The numbers of participants in the control group before and after PS matching were 2061 and 329, respectively. This analysis showed that patient age (adjusted odds ratio [aOR] 1.05; 95% CI 1.01-1.09; P=0.010) and basal FSH level (aOR 1.06; 95% CI 1.01-1.11; P=0.012) were significantly and positively related with the spontaneous follicular growth and ovulation event. In addition, this event was negatively correlated with BMI (aOR 0.92; 95% CI 0.87-0.97; P=0.002), AMH level (aOR 0.66; 95% CI 0.59-0.74; P<0.001) and a high starting oestrogen dose (aOR 0.53; 95% CI 0.38-0.76 for 6mg vs. 4mg; P<0.001). Baseline characteristics were similar between groups after PS matching. Patients in the study group had a significantly higher IR (28.8% vs. 21.8%, P=0.016), CPR (44.9% vs. 33.4%, P=0.011), OPR (39.2% vs. 26.1%, P=0.002) and LBR (39.2% vs. 24.9%, P=0.001) and a lower miscarriage rate (12.7% vs. 25.5%, P=0.030), compared with those in the control group. This was a retrospective study carried out in a single centre and was therefore susceptible to bias. In addition, we only analysed patients with normal ovulation patterns and excluded those with follicular growth but without ovulation. Further studies remain necessary to confirm our results. It is not necessary to cancel cycles that experience spontaneous follicular growth and ovulation. Our data support promising clinical outcomes after this event. Our findings are important as they can better inform clinicians and patients. This research was supported by National Natural Science Foundation of China (grant no. 81701507, 81801404, 81871210, 82071648), Natural Science Foundation of Jiangsu Province (grant no. BK20171126, BK20201123) and Jiangsu Province '333' project. The authors declare that they have no competing interests. N/A.

Impact of Cyproterone Acetate and Ethinylestradiol on Clomiphene Resistant PCOS Patient with High Serum AMH level

Background: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. PCOS is characterized by hyperandrogenism and oligomenorrhea, and Polycystic ovary .It is a common cause of female subfertility. Anti-mullerianhormone (AMH) is 2-4 times higher in patients with PCOS compared to normal subfertilety patient.&#x0D; Objective: To assess the impact of metformin and oral contraceptives (OCs) containing cyproterone acetate and ethinyl estradiol on serum anti-Mullerian hormone (AMH) levels, with CC resistant polycystic ovary syndrome (PCOS)&#x0D; Methods: This prospective randomized controlled trial was conducted at Bangabandhu Sheikh Mujib Medical University(BSMMU), Dhaka during the preoid of January 2019 to june 2019. Already diagnosed patients of polycystic ovary syndrome with subfertility with high serum AMH level more than 5 ng/ml attending in the OPD of Reproductive Endocrinology and infertility department at BSMMU are the study population. Total 60 subjects fulfilling rotardum criteria and who are treated with 3 cycle CC with 100mg /day for 5 days from day 2 of menstrual cycle but fail to ovulate were recruited for the current study. Those subjects with tubal, and male factors excluded from the study. .After enrollment of the patients, randomization will be carried out by blocked randomization method to divide them equally into two groups-Group A number of patients 30 ( treated with2mg cyproterone acetate (CPA) and 35 mcg of ethinylestradiol (EE) and Group B number of patients 30 treated with Metformin). Group A patients will receive treatment with 2mg cyproterone acetate (CPA) and 35 mcg of ethinylestradiol (EE) for 6 months and Group B patients will receive treatment with Metformin for 6 months . After enrollment of the patients, base line hormonal assessment basal level of FSH, LH ,thyroid-stimulating hormone (TSH), prolactin (PRL), and testosterone hormones were registered and metabolic assessment included OGTT and fasting insulin level were done, and to identify the changes in clinical and biochemical profile of study population. Clinical evaluation, by history and examination, transvaginal ultrasonography of both group and changes of the above mentioned parameters of both group were recorded after 6 month of completion of treatment.&#x0D; Results: A Changes in clinical parameters (Acne, BMI, Menestrual cycle) was recorded every three monthly for 6 month. Changes of biochemical parameters (serum LH (D2), serum FSH (D2), serum testosterone, OGTT and fasting insulin), serum AMH were recorded every three monthly for 6 month. Changes of sonographic parameters (ovarian volume, Antral follicular count development, was done monthly for 6 cycles. AMH levels are significantly reduced under treatment with OCP containing 35mg ethinylestradiol plus 2 mg cyproteroneacetate than metformin. AMH was significantly decreased after treatment with 35 mg ethinylestradiol plus 2 mg cyproterone acetate ( p &lt; 0.001 at 6 months). and treatment with metformin did not significantly affect serum AMH levels. AMH was significantly decreased after treatment with metformin (p &lt; 0.005). Serum LH was and OGTT was significantly decreased in both treatment p&lt;0.001.&#x0D; Conclusion(s:) AMH serum levels were significantly decreased under treatment with 35mg ethinylestradiol plus 2mg cyproterone acetate, due to decrease in androgens and suppression of gonadotropins(LH).&#x0D; J Shaheed Suhrawardy Med Coll, December 2020, Vol.12(1); 38-44