Gonadotropin Administration Research Articles

Vitamin D and Vitamin D Receptor in Female Infertility

Objective: To investigate the possible association of serum and follicular fluids(FF) Vitamin D levels with reproductive outcomes after assisted reproductive techniques (ART). Secondly, to detect Vitamin D Receptors (VDR) in serum and follicular fluid (FF) of ovarian follicle and explore its relationship with Vitamin D levels as well as reproductive outcomes.
 Methodology: This study was conducted on May 2019 in Aga Khan Hospital, Karachi, Pakistan. A total of 8 infertile female subjects were conveniently recruited. Serum was collected and follicular fluid(FF) was obtained by transvaginal-guided follicular puncture; 34 hours after intramuscular administration of Human Chorionic Gonadotrophin (HCG). Vitamin D and VDR was assessed in serum as well as in FF by Paired Sample t-test.
 Results: Females 2 out of 8 acquired clinical pregnancy, whereas 3 had pre-clinical abortion or no pregnancy. Vitamin D and VDR were detected highest in those female patients that acquired pregnancy in comparison to the pre-clinical abortion or non-pregnant ones (p value<0.007). Serum VDR did not show any significant results in all groups 
 Conclusion: Vitamin D in serum and FF and vitamin D receptor in serum and FF were associated with number of oocytes. High levels of VDR in FF observed in clinical pregnancy group proved our hypothesis that the presence of VDR in FF is a contributing factor for successful conception after ART success.
 

Progestin primed ovarian stimulation using corifollitropin alfa in PCOS women effectively prevents LH surge and reduces injection burden compared to GnRH antagonist protocol

Utilizing corifollitropin alfa in GnRH antagonist (GnRHant) protocol in conjunction with GnRH agonist trigger/freeze-all strategy (corifollitropin alfa/GnRHant protocol) was reported to have satisfactory outcomes in women with polycystic ovary syndrome (PCOS). Although lessening in gonadotropin injections, GnRHant were still needed. In addition to using corifollitropin alfa, GnRHant was replaced with an oral progestin as in progestin primed ovarian stimulation (PPOS) to further reduce the injection burden in this study. We try to investigate whether this regimen (corifollitropin alfa/PPOS protocol) could effectively reduce GnRHant injections and prevent premature LH surge in PCOS patients undergoing IVF/ICSI cycles. This is a retrospective cohort study recruiting 333 women with PCOS, with body weight between 50 and 70 kg, undergoing first IVF/ICSI cycle between August 2015 and July 2018. We used corifollitropin alfa/GnRHant protocol prior to Jan 2017 (n = 160), then changed to corifollitropin alfa/PPOS protocol (n = 173). All patients received corifollitropin alfa 100 μg on menstruation day 2/3 (S1). Additional rFSH was administered daily from S8. In corifollitropin alfa/GnRHant group, cetrorelix 0.25 mg/day was administered from S5 till the trigger day. In corifollitropin alfa/PPOS group, dydrogesterone 20 mg/day was given from S1 till the trigger day. GnRH agonist was used to trigger maturation of oocyte. All good quality day 5/6 embryos were frozen, and frozen-thawed embryo transfer (FET) was performed on subsequent cycle. A comparison of clinical outcomes was made between the two protocols. The primary endpoint was the incidence of premature LH surge and none of the patients occurred. Dydrogesterone successfully replace GnRHant to block LH surge while an average of 6.8 days of GnRHant injections were needed in the corifollitropin alfa/GnRHant group. No patients suffered from ovarian hyperstimulation syndrome (OHSS). The other clinical outcomes including additional duration/dose of daily gonadotropin administration, number of oocytes retrieved, and fertilization rate were similar between the two groups. The implantation rate, clinical pregnancy rate, and live birth rate in the first FET cycle were also similar between the two groups. In women with PCOS undergoing IVF/ICSI treatment, corifollitropin alfa/PPOS protocol could minimize the injections burden with comparable outcomes to corifollitropin alfa/GnRHant protocol.

Clinical Pregnancy and Incidence of Ovarian Hyperstimulation Syndrome in High Ovarian Responders Receiving Different Doses of hCG Supplementation in a GnRH-Agonist Trigger Protocol.

Objective Ovarian hyperstimulation syndrome (OHSS) is a side effect of the exogenous human chorionic gonadotropin (hCG) hormones used to trigger oocyte maturation. High ovarian responders represent a population with a higher risk of OHSS and are characterized by an exaggerated response to gonadotropin administration. In this study, we compared clinical pregnancy and incidence of OHSS in high ovarian responders receiving different doses of hCG supplementation in a GnRH-agonist trigger protocol. Methods A total of 205 high ovarian responders who were to undergo in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles were recruited and randomly assigned to receive different doses of hCG supplementation in a GnRH-agonist trigger protocol: GnRH-a (n = 42), GnRH-a + 1000 IU hCG (n = 49), GnRH-a + 2000 IU hCG (n = 54), and GnRH-a + 3000 IU hCG (n = 60) groups. Results The GnRH-a + 1000 IU hCG, GnRH-a + 2000 IU hCG, and GnRH-a + 3000 IU hCG groups had more oocytes retrieved, embryos, high-quality embryos, and a higher rate of high-quality embryos than the GnRH-a group (p < 0.05). The GnRH-a + 1000 IU hCG group demonstrated more oocytes retrieved, embryos, high-quality embryos, and a higher rate of high-quality embryos than the GnRH-a + 2000 IU hCG and GnRH-a + 3000 IU hCG groups (p < 0.05). No moderate and severe OHSS cases occurred in the GnRH-a and GnRH-a + 1000 IU hCG groups. The incidence rate of moderate and severe OHSS was remarkably lower in the GnRH-a group and GnRH-a + 1000 IU hCG groups than in the GnRH-a + 2000 IU hCG and GnRH-a + 3000 IU hCG groups (p < 0.05). The GnRH-a + 1000 IU hCG, GnRH-a + 2000 IU hCG, and GnRH-a + 3000 IU hCG groups had a higher clinical pregnancy rate than the GnRH-a group, showing no significant difference (p > 0.05). The GnRH-a + 1000 IU hCG, GnRH-a + 2000 IU hCG, and GnRH-a + 3000 IU hCG groups had a lower abortion rate than the GnRH-a group (p < 0.05). Conclusion Based on the data obtained from this prospective study, we recommend 1000 IU hCG supplementation in a GnRH-agonist trigger protocol for high ovarian responders during IVF/ICSI cycles considering a higher rate of high-quality embryos, a lower incidence rate of moderate and severe OHSS, and a lower abortion rate.

Daily variation of the cortisol and insulin concentration, glycemia, surface temperature, and behavior patterns due the administration of equine Chorionic Gonadotropin in rams

Sex steroids can modulate the circadian rhythmicity of some physiological and behavioral functions of sheep. During the non-breeding season, Corriedale rams have a low testosterone concentration, but the administration of equine Chorionic Gonadotropin (eCG) stimulates its secretion. Therefore, the daily variation of cortisol and insulin concentrations, glycemia, behavioral pattern (eating, ruminating, standing, lying, and sleeping), and rostral and eye surface temperatures were compared in rams treated or not treated with eCG during the non-breeding season [between August (late winter) and September (early spring)]. Twenty Corriedale adult rams (BW 63.4 ± 7.3 kg; BCS: 3.5 ± 0.5; mean ± SD; age: 2-3 years old) were randomly assigned to 1 of 2 treatments: a) Treated: administration of 1000 IU of eCG intramuscularly and b) Control: control, without application of eCG. All the rams were managed under the same feeding and environmental conditions (individual pens outdoors). All variables were measured each hour for 26 h, except testosterone and insulin that were measured at 09:00, 10:00, 12:00, 15:00, 18:00, 21:00, 22:00, 24:00, 03:00, 06:00, 09:00 and 11:00 h. Testosterone and cortisol concentration were greater in Treated than Control rams (testosterone: 32.7 ± 0.7 nmol/L vs 5.8 ± 0.7 nmol/L; P <0.0001; cortisol: 11.3 ± 0.6 nmol/L vs 9.9 ± 0.6 nmol/L; P =0.02). The eye surface temperature was 0.9°C lower in the Treated than in the Control rams (P =0.004). The characteristics of the daily variation pattern of cortisol, glycemia, glycemia:insulin ratio, and surface temperature were not affected by the treatment, the acrophases being at ∼06:00 h, ∼18:00 h, ∼08:00 h, and ∼11:00 h, respectively. The acrophase of insulin concentration was observed earlier in Treated than in Control rams (13:02 ± 0:56 vs 15:47 ± 0:53; P =0.04). Additionally, the acrophase of the time spent eating was advanced in Treated rams (09:48 ± 00:16 vs 10:20 ± 00:16; P =0.04) and sleeping (21:39 ± 00:57 vs 02:02 ± 01:06; P <0.0001). Treated rams slept less time than Control rams (P =0.04). In conclusion, the administration of eCG modulated the daily variation pattern of insulin concentration and the behavioral pattern (period in which rams were observed eating and sleeping). Nevertheless, although there was a greater cortisol concentration and reduced eye surface temperature, the administration of eCG did not modify their daily variation pattern, suggesting that this is robust, limiting the effect of testosterone on their basal pattern.

Nomogram to predict pregnancy outcomes of emergency oocyte freeze-thaw cycles.

Background:Existing clinical prediction models for in vitro fertilization are based on the fresh oocyte cycle, and there is no prediction model to evaluate the probability of successful thawing of cryopreserved mature oocytes. This research aims to identify and study the characteristics of pre-oocyte-retrieval patients that can affect the pregnancy outcomes of emergency oocyte freeze-thaw cycles.Methods:Data were collected from the Reproductive Center, Peking University Third Hospital of China. Multivariable logistic regression model was used to derive the nomogram. Nomogram model performance was assessed by examining the discrimination and calibration in the development and validation cohorts. Discriminatory ability was assessed using the area under the receiver operating characteristic curve (AUC), and calibration was assessed using the Hosmer–Lemeshow goodness-of-fit test and calibration plots.Results:The predictors in the model of “no transferable embryo cycles” are female age (odds ratio [OR] = 1.099, 95% confidence interval [CI] = 1.003–1.205, P = 0.0440), duration of infertility (OR = 1.140, 95% CI = 1.018–1.276, P = 0.0240), basal follicle-stimulating hormone (FSH) level (OR = 1.205, 95% CI = 1.051–1.382, P = 0.0084), basal estradiol (E2) level (OR = 1.006, 95% CI = 1.001–1.010, P = 0.0120), and sperm from microdissection testicular sperm extraction (MESA) (OR = 7.741, 95% CI = 2.905–20.632, P < 0.0010). Upon assessing predictive ability, the AUC for the “no transferable embryo cycles” model was 0.799 (95% CI: 0.722–0.875, P < 0.0010). The Hosmer–Lemeshow test (P = 0.7210) and calibration curve showed good calibration for the prediction of no transferable embryo cycles. The predictors in the cumulative live birth were the number of follicles on the day of human chorionic gonadotropin (hCG) administration (OR = 1.088, 95% CI = 1.030–1.149, P = 0.0020) and endometriosis (OR = 0.172, 95% CI = 0.035–0.853, P = 0.0310). The AUC for the “cumulative live birth” model was 0.724 (95% CI: 0.647–0.801, P < 0.0010). The Hosmer–Lemeshow test (P = 0.5620) and calibration curve showed good calibration for the prediction of cumulative live birth.Conclusions:The predictors in the final multivariate logistic regression models found to be significantly associated with poor pregnancy outcomes were increasing female age, duration of infertility, high basal FSH and E2 level, endometriosis, sperm from MESA, and low number of follicles with a diameter >10 mm on the day of hCG administration.

THE USE OF OVULATION PREDICTOR KITS FOR DONOR SPERM INSEMINATION CYCLES: THE DATA IS CLEAR

Studies have demonstrated that patient interpretation of home urinary ovulation predictor kits (OPKs) not uncommonly results in false-positive tests (McGovern PG et al., Fertil Steril 2004 Nov;82(5):1273-7). Patients undergoing donor sperm intrauterine insemination (IUI-D) typically have one opportunity for exposure to sperm during a treatment cycle, making the timing of IUI-D critical. We therefore undertook a Quality Improvement project investigating whether patients undergoing IUI-D had different success rates when IUI-D was timed 24-32 hours after positive morning OPK or 24-32 hours after clinic administration of Human Chorionic Gonadotropin (HCG).

WS-5. Proposal for a novel classification based on onset of HDP; antenatal onset, labor onset, and postpartum onset

Elevated progesterone on the day of human chorionic gonadotropin (hCG) administration is associated with decreased live birth rates in IVF cycles. The association with adverse pregnancy outcomes is unknown.Assess the association between serum progesterone on the day of hCG administration and the risk of ischemic placental disease [IPD; preeclampsia, placental abruption, and/or small for gestational age (SGA)].We conducted a retrospective cohort study of autologous fresh IVF cycles resulting in delivery between 2005 and 2018. All IVF procedures were conducted at a large, university-affiliated infertility center. Patients were divided into tertiles based on their serum progesterone level on the day of hCG administration; the lowest tertile served as the reference group. We identified pregnancies complicated by preeclampsia and placental abruption using ICD-9/10 codes and medical record review. We defined SGA as < 10th percentile using U.S. growth curves.The cohort included 166 deliveries in the lowest tertile of progesterone (0.2–0.73 ng/ml), 166 deliveries in the middle (0.64–1.05 ng/ml) and 167 deliveries in the highest tertile (1.05–5.6 ng/ml). Compared with the lowest tertile, the risk of IPD was greater in the middle (RR 1.6; 95% CI 1.1–2.5) tertile after adjustment for age, parity, number of oocytes retrieved, and estradiol. The highest tertile was also not associated with an increased risk of IPD.In an IVF population, elevated serum progesterone in the range of 0.64–1.05 ng/mL on the day of hCG administration was associated with a small increased risk of IPD.

Microdose Flare-up Gonadotropin-releasing Hormone (GnRH) Agonist Protocol and GnRH Antagonist Protocol: Effects on In-vitro Fertilization in Patients with Poor-responder Diagnosis According to Bologna Criteria

Objective: The aim of the study was to evaluate microdose flare-up Gonadotropin-Releasing Hormone (GnRH) agonist protocol and GnRH antagonist protocol with respect to their effects on in-vitro fertilization (IVF) results in patients with poor ovarian response according to the Bologna Criteria.&#x0D; Material Methods: This was a retrospective cohort study conducted in the Assisted Reproduction clinic of University of Health Sciences, Etlik Zübeyde Hanım Gynaecology Training and Research Hospital. A total of 645 patients who had been diagnosed as poor responders in our clinic, between 2007 and 2018, and received treatment with either microdose flare-up GnRH agonist protocol (n=250, 38.8%) or GnRH antagonist protocol (n=395, 61.2%), were included in the study.&#x0D; Results: The mean age of the study group was 34.5±5.5 years. Comparisons showed that IVF cycle cancellation frequency (p&lt;0.01), third day estradiol level (p=0.04) and third day follicle stimulating hormone level (p&lt;0.01) were significantly greater in patients who underwent the microdose flare-up protocol. In the GnRH antagonist group, the number of surviving children (p=0.01), antral follicle count (p&lt;0.01), follicle count on day of human chorionic gonadotropin (hCG) administration (p&lt;0.01), endometrial thickness on hCG day (p&lt;0.01), number of oocytes collected (p&lt;0.01), mature oocyte count (p&lt;0.01), embryo transfer number (p&lt;0.01) were higher compared to the microdose flare-up protocol group. The two groups were similar in terms of clinical pregnancy rate.&#x0D; Conclusions: In terms of clinical pregnancy rate, the IVF results of microdose flare-up and GnRH antagonist protocols are similar. Further studies are needed to reach more comprehensive results on the subject.

Evaluation of the relationship between serum estradiol levels on human chorionic gonadotropin administration day and intracytoplasmic sperm injection outcomes: A retrospective population-based study.

BackgroundThe correlation between high estradiol (E2) levels induced by controlled ovarian hyperstimulation (COH) and pregnancy is controversial.ObjectiveTo assess the effect of serum E2 levels on the day of human chorionic gonadotropin administration on the intracytoplasmic sperm injection (ICSI) outcome.Materials and MethodsThe current study included 551 participants who had undergone ICSI between May 2014 and May 2016. Based on E2 levels, the individuals aged 37 yr (n = 502) and 37-42 yr (n = 49) were categorized into six and three groups, respectively. ICSI outcomes including the number of retrieved oocytes (NRO), number of embryos (NE), pregnancy rate, and abortion rate were analyzed in both groups.ResultsAmong participants aged 37 yr, the NRO and NE were 8.69 3.82 and 5.24 2.32, respectively and they had a significant correlation with the E2 level on human chorionic gonadotropin administration day (p 0.001 for both). Among participants aged 37 yr, NRO and NE were 5.18 3.17 and 3.40 2.23, respectively, and the NRO (p 0.001), NE (p 0.001), pregnancy rate (p 0.001), abortion rate (p = 0.007), and the number of grade A and B embryos (p = 0.003) had a significant association with the E2 level.ConclusionCOH is a costly procedure that may have negative effects on endometrial receptivity. Thus, in order to prevent these effects and also to reduce the costs of COH, we recommend gaining optimum number of oocytes rather than maximum number during the procedure.

Ovulatory upregulation of angiotensin-converting enzyme 2, a receptor for SARS-CoV-2, in dominant follicles of the human ovary

ObjectiveTo determine the temporal expression of angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV-2, in dominant follicles throughout the periovulatory period in women and the regulatory mechanisms underlying ACE2 expression in human granulosa/lutein cells (hGLC).DesignExperimental prospective clinical study and laboratory-based investigation.SettingUniversity Medical Center and private in vitro fertilization center.Patient(s)Thirty premenopausal women undergoing surgery for tubal ligation and 16 premenopausal women undergoing in vitro fertilization.Intervention(s)Administration of human chorionic gonadotropin (hCG) and harvesting of preovulatory/ovulatory follicles by timed laparoscopy, and collection of granulosa/lutein cells and cumulus cells at the time of oocyte retrieval.Main Outcome Measure(s)Expression and localization of ACE2 in granulosa cells and dominant follicles collected throughout the periovulatory period of the menstrual cycle and in hGLC using quantitative polymerase chain reaction, immunoblotting, and immunohistochemistry.Result(s)ACE2 expression (mRNA and protein) is up-regulated in human ovulatory follicles after administration of hCG. ACE2 expression was higher in cumulus cells than in granulosa cells. hCG increased the expression of ACE2 in primary hGLC cultures; the increase was inhibited by RU486 (an antagonist for progesterone receptor and glucocorticoid receptor) and CORT125281 (a selective glucocorticoid receptor antagonist), but not by AG1478 (an EGF receptor tyrosine kinase inhibitor) or by dexamethasone.Conclusion(s)The hormone-regulated expression of ACE2 in granulosa cells suggests a potential role of ACE2 in the ovulatory process. These data also imply the possible impact of COVID-19 on a vital cyclic event of ovarian function and thus on women's overall reproductive health. However, SAR-CoV-2 infection in ovarian cells in vivo or in vitro has yet to be determined.

P–309 Effectiveness of intrauterine infusion of platelet-rich plasma (PRP) vs. granulocyte colony-stimulating factor (G-CSF) in women with thin endometrium undergoing assisted reproduction

Abstract Study question To compare the effect of intrauterine infusion of platelet-rich plasma (PRP) and granulocyte colony-stimulating factor (G-CSF) on endometrial thickness, clinical pregnancy rate and live-birth rate. Summary answer According to our research, PRP-therapy has more positive results in pregnancy rates. Nevertheless, there is still limited data to answer all questions completely. What is known already Thin endometrium is defined as endometrium thickness &amp;lt;7 mm or &amp;lt; 8 mm on the day of human chorionic gonadotropin (HCG) administration, which negatively affects the onset of pregnancy during natural fertilization and in assisted reproduction. Endometrial thickness may impact pregnancy and live-birth rates in fresh and frozen IVF cycles but, currently, there is minimal evidence to support any specific protocol to significantly improve pregnancy outcomes in patients with thin endometrium. Therefore, we decided to compare effects of two methods: transvaginal intrauterine perfusion of G-CSF for infertile women with thin endometrium in IVF cycles and intrauterine infusion of PRP. Study design, size, duration We conducted a systematic review and meta-analysis by PRISMA checklist. PubMed, The Cochrane Library, ClinicalTrials.gov and Google Scholar were searched electronically until 2021 using key words: “G-CSF”, “PRP”, “endometrium”. We included published and unpublished randomized clinical trials (RCT) and non-randomized clinical trials in English which include min.10 patients. Participants/materials, setting, methods Participants: female infertile patients of reproductive age with thin endometrium (≤ 7 mm) in embryo transfer cycles. Exclusion criteria: history of any chromosomal or genetic abnormalities and hematological disorders. Outcomes – endometrial thickness, pregnancy and live-birth rates.Risk of bias assessment was held using The Cochrane Handbook and The Cochrane collaboration tools. RoB 2 tool was used for randomized trials and ROBINS-I tool for non-randomized trials. For quantitative synthesis RevMan 5.4 was used to conduct meta-analysis. Main results and the role of chance Literature search resulted in 144 potentially relevant publications initially (Google Scholar: 126, PubMed: 1, Clinicaltrials: 14, Cochrane: 3). These publications were checked for titles and abstracts, duplicates were removed and 7 publications were selected. After evaluating the selection criteria, 2 articles were excluded. As a result, 5 articles remained for qualitative and quantitative synthesis, including 2 randomized controlled trials (RCT), 2 retrospective cohort studies, and 1 prospective cohort study. 403 patients participated in selected studies (the PRP group included 205 patients, and the G-CSF group - 198 patients). The primary quantitative analysis (meta-analysis) is aimed at comparison of endometrial thickness in patients receiving PRP therapy and patients receiving G-CSF. Two RCTs were included in this meta-analysis. (RR = 1.07, 95% CI: 0.81 to 1.43, P = 0.63). The heterogeneity for this comparison was 0%. Consequently, both options are equally altered by the thickness of endometrium. The secondary analysis compared clinical pregnancy rates in patients receiving PRP therapy and G-CSF. 4 studies were eligible for this synthesis. (RR = 1.36, 95% Cl: 1.06 to 1.76, P = 0.02). The heterogeneity for this comparison was 55%. PRP was significantly more effective. Limitations, reasons for caution Firstly, only 5 publications were found for the entire time. There are not enough well-conducted studies for more accurate analysis. Secondly, according to risk of bias assessment most of included studies had moderate concerns. Finally, there is no sufficient data to judge about live-birth rates after both types of treatment. Wider implications of the findings: Thin endometrium negatively affects the onset of pregnancy in assisted reproduction.Based on our meta-analysis, PRP therapy has a considerable effect on pregnancy rates in patients with thin endometrium in comparison with G-CSF.Currently, there is minimal evidence to support any specific protocol for improving IVF outcomes in women with thin endometrium. Trial registration number PROSPERO 2020 CRD42020222075

P–246 Oocyte degeneration after ICSI is not an indicator of live birth in young women

Abstract Study question To investigate whether oocyte degeneration after intracytoplasmic sperm injection (ICSI) is an indicator for predicting the cumulative live birth rate. Summary answer The presence of oocyte degeneration after ICSI is not an indicator for predicting the cumulative live birth rate per OPU cycle in young women. What is known already Oocyte degeneration may be associated with decreased embryo quality for embryo development kinetics was disturbed. No differences in clinical outcomes such as implantation rate or clinical pregnancy rate were found in fresh embryo transfer cycles in retrospective studies. Study design, size, duration This was a retrospective cohort study, including all the oocyte retrieval cycles from young women who underwent ICSI from January 2018 to December 2019 at the Reproductive Medicine Center of the First Affiliated Hospital of Sun Yat-sen University. Participants/materials, setting, methods The inclusion criteria were as follows: female age was younger than 35 years; the first or second oocyte retrieval cycles ;the number of oocyte retrieval was between 8 and 20; all the cycles performed fresh embryo transfer on day 3 after insemination. Cycles with at least one oocyte degenerated after ICSI were defined as the oocyte degeneration group (OD group), and cycles with no oocyte degenerated after ICSI were defined as the non-OD group Main results and the role of chance There were no significant differences with regards to implantation rate (38.5% vs 35.1%, P = 0.302), clinical pregnancy rate (54.9% vs 50.3%, P = 0.340), and live birth rate per OPU cycle (47.0% vs 42.9%, P = 0.395) between OD and non-OD groups. Initial gonadotropin dosage, E2 level on hCG day and the number of matured oocytes appeared to be independent risk factors for OD, after adjustment for female age, female BMI, duration of gonadotropin administration, FORT, number of retrieved oocytes and different technicians. The adjusted odds ratio of live birth rate per OPU cycle were similar in subgroups with different oocyte degeneration rates. The ongoing pregnancy/live birth rate per transfer in FET cycles was not significantly different between OD group and non-OD groups (38.8% vs 43.9%, P = 0.439). The cumulative live birth rate per OPU cycle was also comparable between the OD group and non-OD group (63.4% vs 64.8%, P = 0.760). Limitations, reasons for caution The time interval for the follow-up was not long enough for all the frozen embryos to be transferred. Moreover, the retrospective nature of the study introduces the potential to include confounding variables that may bias our results, although we performed multiple logistic regression analysis to minimize these effects. Wider implications of the findings: The presence of oocyte degeneration is not an indicator for predicting the cumulative live birth rate per OPU cycle in young women. Initial gonadotropin dosage, E2 level on hCG day and the number of matured oocytes appeared to be independent risk factors for oocyte degeneration. Trial registration number none

A Case Report: Infertility Treatment of a Female with Beta-thalassemia Major

Beta-thalassemia is caused by a genetically mediated deletion of beta-globin chain of hemoglobin. It is an autosomal recessive disease, which causes a severe medical condition that requires longterm blood transfusions. An impaired hypothalamic-pituitary-ovarian axis mainly causes infertility in such patients. This case report presents a 26-year-old female, a known case of beta-thalassemia major, that received monthly blood transfusions before conceiving. The patient sought consultation for the treatment of primary infertility at Bahrain Defence Force Royal Medical Services (BDF-RMS) Hospital. The patient underwent two trials of intrauterine insemination (IUI). The goal was to build up endometrial thickness by gonadotrophins administration for embryo implantation. To conclude, IUI combined with gonadotrophins for ovarian stimulation has shown success. Keywords: Artificial Insemination, Beta-Thalassemia, Hypogonadism, Infertility, Pregnancy

Analysis of endometrial thickness patterns and pregnancy outcomes considering 12,991 fresh IVF cycles

BackgroundDifferent endometrial patterns have an important effect on the relationship between endometrial thickness (EMT) and clinical pregnancy rate. There is a significant difference in age, selection of cycle protocols, and clinical pregnancy rates among four groups with diverse endometrial patterns.MethodsThis retrospective study aimed to assess the association between EMT on human chorionic gonadotropin (HCG) administration day and the clinical outcome of fresh in vitro fertilization (IVF). The 5th, 50th, and 95th percentiles for EMT were determined as 8, 11, and 14 mm, respectively. Patients were sub-divided into four groups based on their EMT in different endometrial patterns (Group 1: < 8 mm; Group 2: ≥ 8 and ≤ 11 mm; Group 3: > 11 and ≤ 14 mm; Group 4: > 14 mm). We divided patients into three groups based on their endometrial pattern and evaluated the correlation between EMT and clinical pregnancy rate.ResultsWe found a positive correlation between pregnancy rates and EMT in all endometrial patterns. Multiple logistic regression analysis proved age, duration of infertility, cycle protocols, number of embryos transferred, progesterone on HCG day, endometrial patterns, and EMT have significant effects on clinical pregnancy rates. Meanwhile, there was a significant difference in age, selection of cycle protocols, and clinical pregnancy rates among four groups with diverse endometrial patterns.ConclusionsDifferent endometrial patterns have an important effect on the relationship between EMT and clinical pregnancy rate.

Female fertility preservation: Impact of cancer on ovarian function and oocyte quality.

To evaluate the influence of cancer on ovarian response and oocyte quality in controlled ovarian hyperstimulation (COH). This prospective study conducted at the Physiopathology of Reproduction and Andrology Unit of Sandro Pertini Hospital enrolled 82 cancer patients undergoing controlled ovarian stimulation (COH) cycles for fertility preservation, and age- and date-matched controls undergoing COH for in vitro fertilization for male-factor infertility from June 2016 to November 2019. The interventions performed were COH, oocyte retrieval, and quality evaluation. Main outcome measures were maximal estradiol levels on the day of human chorionic gonadotropin administration, duration of stimulation, total amount of gonadotropins administered, number of oocytes retrieved, and rates of metaphase 2 oocytes and abnormal oocytes. All data were analyzed using the Statistical Package for the Social Sciences (IBM Corp., Armonk, NY, USA) 22.0. Intergroup comparisons (82 cancer patients and 180 patients in control group) showed a significant difference in ovarian response, especially for a significant higher number of abnormal oocytes in cancer patients (P<0.0001). Regression analysis to assess the influence of the neoplastic process, regardless of the type, on ovarian response showed an effect on the main outcome measured due to cancer itself. Cancer influences the ovarian response, particularly the oocyte quality, during COH performed for fertility preservation.

Impact of preconceptional serum thyroid stimulating hormone values ranging between 2.5 and 4.5 mIU/L on live birth rates following ovulation induction and intrauterine insemination treatment for unexplained infertility

BackgroundContrary to overt hypothyroidism, the true impact of subclinical hypothyroidism on fertility has not been well established. This study aimed to investigate whether serum thyroid stimulating hormone (TSH) values between 2.5 and 4.5 mIU/L are associated with lower pregnancy rates compared to TSH levels between 0.3 and 2.5 mIU/L in women undergoing ovulation induction with gonadotropins and intrauterine insemination (IUI) for unexplained infertility.MethodsMedical records of couples with unexplained infertility who underwent IUI treatment between January 2013 and December 2018 were reviewed retrospectively. Cycle characteristics and pregnancy outcomes of patients with serum TSH levels between 0.3–2.5 mIU/L and 2.5–4.5 mIU/L were compared. Primary outcome measures were clinical pregnancy and live birth rate. Secondary outcome measures were total dose of gonadotropin administration, duration of ovulation induction and miscarriage rate.ResultsA total of 726 euthyroid women who underwent 1465 cycles of ovulation induction with gonadotropins and IUI were included in the analyses. Patient and cycle characteristics of the two study groups were similar. No statistically significant differences could be detected in the clinical pregnancy (p = 0.74) and live birth rates (p = 0.38) between the two groups. Duration of ovulation induction, total gonadotropin dosage, number of follicles > 17 mm on the trigger day and the miscarriage rates were similar in the two groups.ConclusionIn euthyroid women undergoing ovulation induction with gonadotropins and IUI for unexplained infertility, the range of preconceptional serum TSH values between 2.5 and 4.5 mIU/L is not associated with lower pregnancy rates when compared to TSH levels between 0.3 and 2.5 mIU/L.

Precocious pseudo-puberty in a 2-year-old girl, presenting with bilateral ovarian enlargement and progressing to unilateral juvenile granulosa cell tumour

Ovarian causes of precocious pseudo-puberty (PPP) include McCune-Albright syndrome (MAS) and juvenile granulosa cell tumour (JGCT). We describe a case of PPP in which bilateral ovarian enlargement with multiple cysts progressed to unilateral JGCT. A girl aged 2.17 years presented with 3 months of breast development, and rapid growth. Examination showed tall stature, height + 2.6 standard deviations, Tanner stage B3P2A1. A single cafe au lait patch was noted. Bone age was advanced at 5 years. Pelvic ultrasound showed bilaterally enlarged ovaries (estimated volumes 76 ml on the left, 139 ml on the right), each containing multiple cysts. Luteinizing hormone (LH) and follicle stimulating hormone (FSH) values before/after gonadotrophin administration were 0.43/0.18 and < 0.1/<0.1 mUI/ml, serum estradiol 130 pg/ml, (prepubertal range < 20). PPP of ovarian origin was diagnosed, and Tamoxifen 20 mg daily started. However, after only 7 weeks height velocity escalated and breast development increased to B3-4 with menorrhagia. Basal/stimulated LH and FSH were still suppressed at 0.13/0.25 and <0.1/<0.1 mUI/ml, serum estradiol 184 pg/ml. Repeat imaging now showed normal right ovary (volume 1.8 ml) and a large left-sided vascular solid/cystic ovarian tumour which was excised (weight 850g). Histology showed JGCT, FIGO stage IA. DNA from tumour tissue showed no mutation in GNAS, exon 3 of AKT1 (which contains a mutational hotspot) or FOXL2. The observation that bilateral ovarian activity progressed to unilateral development of JGCT in this patient is novel. This case highlights current uncertainties in the ontology of JGCT, and its possible relationship with MAS.

Proof of concept use of progesterone/estradiol ratio to investigate late follicular progesterone in women with low number of preovulatory follicles.

The aim of this study was to investigate late follicular progesterone (P) serum levels in women with a low number of preovulatory follicles in the assisted reproductive technologies (ART) setting. Fifty-five consecutive women having four or fewer preovulatory follicles of >14 mm on the day of human chorionic gonadotropin (hCG) administration were prospectively evaluated. Spearman correlation tests were performed between serum estradiol (E<inf>2</inf>) level, serum P level, P/E<inf>2</inf> ratio, number of preovulatory follicles, oocytes and embryos. Women enrolled were further divided into two groups in accordance with the P/E<inf>2</inf> ratio on the day of hCG administration and compared. Serum E<inf>2</inf> level correlated positively with P serum level (r<inf>s</inf>=0.36, P<0.01), number of mature follicles (r<inf>s</inf>=0.50, P<0.01) and number of oocytes retrieved (r<inf>s</inf>=0.36, P<0.05), whereas negatively with P/E<inf>2</inf> ratio (r<inf>s</inf>=- 0.68, P<0.01). Likewise, number of preovulatory follicles correlated positively with E<inf>2</inf> level (r<inf>s</inf>=0.50, P<0.01), P level (r<inf>s</inf>=0.27, P<0.05) and number of oocytes retrieved (r<inf>s</inf>=0.33, P<0.05), while it correlated negatively with P/E<inf>2</inf> ratio (r<inf>s</inf>=-0.33, P<0.05). Furthermore, women with P/E<inf>2</inf> ratio >1 on the day of hCG administration received considerably higher total follicular stimulating hormone (FSH) dosage and achieved significantly lower number of oocytes and embryos as compared to controls. The reverse relationship between number of preovulatory follicles and P/E<inf>2</inf> ratio implies that P rise is not only the result of increased steroidogenic activity, but other oocyte-follicle disrupted mechanisms seem to be involved. An exaggerated FSH stimulation appears to disrupt further these mechanisms.

The value of serum progesterone level on day of human chorionic gonadotrophin administration / metaphase II oocyte ratio in predicting IVF/ICSI outcome in patients with normal ovarian reserve

BackgroundThe clinical implication of the increased serum progesterone level on the day of HCG administration in assisted reproduction treatment (ART) is still controversial. The current study aimed to compare the predictive value of serum progesterone on day of HCG administration / metaphase II oocyte (P/MII) ratio on IVF/ ICSI outcome to serum progesterone (P) level alone and the ratio of serum progesterone/estradiol level (P/E2) ratio in prediction of pregnancy rates after ART.Material & methodsTwo hundred patients admitted to the IVF/ICSI program at Minia IVF center in Egypt in the period from October 2016 to May 2018 were included in this study. Serum Progesterone (P) and Estradiol (E2) levels were estimated on the day of HCG administration. The ratio between serum P and the number of MII oocytes (P/MII ratio) was calculated and the predictive values of the three parameters (P, P/E2 ratio and P/MII ratio) in prediction of cycle outcomes were measured.ResultsP/ MII oocyte ratio was significantly lower in patients who attained clinical pregnancy (n = 97) as compared with those who couldn’t whilst there was no significant difference in P and P/E2 ratio between the two groups. Using a cut off value of 0.125, the sensitivity and specificity of progesterone/ MII ratio in prediction of no pregnancy in IVF/ICSI were 75.7 and 77.1% respectively with the area under The Receiver operating curve (ROC-AUC) = 0.808. The respective values of the ROC-AUC for the P and P/E2 ratio were 0.651 and 0.712 with sensitivity and specificity of 71.2 and 73.5%for P level and of 72.5 and 75.3% for P/E2 ratio. Implantation or clinical pregnancy rates were significantly different between patients with high and low P/MII ratio irrespective of day of embryo transfer (day 3 or 5).ConclusionsIn patients with normal ovarian response, serum progesterone on day of HCG / MII oocyte ratio can be a useful predictor of pregnancy outcomes and in deciding on freezing of all embryos for later transfer instead of high progesterone level alone.

Resumed ovarian function and pregnancy in early menopausal women by whole dimension subcortical ovarian administration of platelet-rich plasma and gonadotropins.

This study was designed to investigate if whole dimension subcortical ovarian administration of platelet-rich plasma with gonadotropin, in proximity to most ovarian follicles, is effective in restoring ovarian functions in women during early menopause. Platelet-rich plasma, prepared from 40 mL of autologous peripheral blood using the buffy coat method, was injected into extended subcortical area of bilateral ovaries along with recombinant follicle-stimulating hormone (rFSH) (Gonal-F 300IU) under laparoscopic guidance. The posttreatment ovarian folliculogenesis and serum levels of FSH, luteinizing hormone (LH), and estradiol were followed up for 6 months at weekly to monthly intervals. IVF was carried out in women resuming ovulatory functions. Twelve early menopausal women with mean age of 44.42 ± 2.84 were enrolled. After treatment, 11 women resumed their menstrual period in 37.1 ± 23.5 days. Their average serum FSH was 70.47 ± 20.92 and 26.22 ± 17.55 IU/L, luteinizing hormone was 34.81 ± 11.86 and 14.3 ± 12.8 IU/L, before and after treatment, respectively. The mid-cycle E2 was 251.1 ± 143.8 pg/mL. Ten oocyte retrievals were carried out among six participants, four of them received controlled ovarian stimulation and another two using natural ovulation cycles. Thirteen mature eggs were retrieved which were then ICSI fertilized to obtain 10 normally fertilized 2PN oocytes. Two participants had cleavage stage embryos transferred of which one achieved clinical pregnancy. Whole dimension subcortical ovarian administration of platelet-rich plasma with gonadotropin was shown to restore ovarian functions, at least temporarily, and could increase the probability of pregnancy using autologous oocytes in women with early menopause.