Human Chorionic Gonadotropin Trigger Research Articles

Do basal Luteinizing Hormone and Luteinizing Hormone/Follicle-Stimulating Hormone Ratio Have Significance in Prognosticating the Outcome of In vitro Fertilization Cycles in Polycystic Ovary Syndrome?

Context:Tonic hypersecretion of luteinizing hormone (LH) appears to impact both fertility and pregnancy outcomes in women with polycystic ovary syndrome (PCOS).Aim:Whether high basal day 2/3 serum LH levels and day 2/3 LH/follicle-stimulating hormone (FSH) ratio affect in vitro fertilization (IVF) cycle outcomes in PCOS patients undergoing controlled ovarian hyperstimulation using gonadotropin-releasing hormone (GnRH) antagonists.Settings and Design:A retrospective cohort study was conducted in Assisted Reproductive Technique Center, Department of Obstetrics and Gynaecology, at a tertiary care institute, on PCOS patients undergoing IVF/intracytoplasmic sperm injection (ICSI) using GnRH antagonist protocol with human chorionic gonadotropin trigger between January 2014 to December 2019.Methods and Material:Data related to patient's age, body mass index, day 2/3 serum FSH, serum LH, day 2/3 LH/FSH ratio, and infertility treatment-related variables were collected from the patient record files. IVF cycle characteristics, number of oocytes retrieved, number of embryos transferred were also recorded. The clinical pregnancy rate per embryo transfer was calculated.Statistical Analysis:Statistical software SPSS IBM version 24.0 was used to analyze the data. Descriptive statistics such as mean, standard deviation , and range values were calculated. To compare the difference between the groups, the paired t-test was applied for continuous variables and the Chi-square test for categorical variables. A value of P < 0.05 was considered statistically significant.Results:High basal day 2/3 LH level and day 2/3 LH/FSH ratio have no statistically significant effect on embryos formed, embryo transferred, and clinical pregnancy rate. However, fertilization rates were significantly less in these groups.Conclusion:The elevated basal day 2/3 LH and LH/FSH ratio do not impair the outcome of GnRH antagonist protocol treated IVF/ICSI cycles in PCOS women.

The predictive value of endometrial thickness for assessing neonatal birth weight in ART

Background: Neonatal birth weight is lower after assisted reproductive technology (ART) conception compared with natural conception. The aim of this retrospective study was to evaluate the predictive potential of measuring maternal endometrial thickness (ET) in women undergoing ART for assessing neonatal birth weight. Methods: and Results The patients (n = 100) were screened for meeting inclusion criteria with primary or secondary infertility and who underwent In-vitro Fertilization/Intracytoplasmic sperm injection (IVF/ICSI) or frozen embryo transfer (FET) cycles were enrolled in the study. All women received the antagonist protocol with recombinant gonadotropins/urinary gonadotropins or human menopausal gonadotropin as a stimulation protocol. Only singleton pregnancies were used in neonatal birth weight (n = 70) measurements. Retrospective data were collected for age, body mass index (BMI), and ET done by two-dimensional ultrasound that had successful pregnancy. The antenatal details, birth weight/gender of neonates were noted. A univariate regression analysis was performed between ET and neonatal birth weight in patients with live births (n = 70) to evaluate association between these parameters. The data were adjusted for variables such as age, BMI, and gestational duration. There was significant association of ET with neonatal birth weight and ET was observed to be a significant independent predictor for neonatal birth weight (slope 0.168, P = 0.0052). Conclusion: The present study suggests that ET measurement at the time of human chorionic gonadotropin (hCG) trigger in Indian women undergoing ART cycles can be a reliable independent predictor for assessing neonatal birth weight

To Compare the Effect of GnRH Agonist versus Human Chorionic Gonadotropin (HCG) Trigger on Clinical Pregnancy Rate in Intrauterine Insemination Cycle.

Context:Gonadotropin-releasing hormone (GnRH) agonist trigger mimics the natural surge more closely with both luteinizing hormone (LH) and follicle-stimulating hormone surge. The present study attempts to find whether this apparent physiological advantage translates into the better pregnancy rate.Aims:To compare the effect of GnRH agonist versus human chorionic gonadotropin (hCG) trigger on the clinical pregnancy rate (CPR) in infertile women undergoing intrauterine insemination (IUI) with oral ovulogens.Settings and Design:Retrospective analysis at a tertiary care in vitro fertilization center.Materials and Methods:The records of 280 infertile women, who underwent IUI with oral ovulogens were analyzed. Women who received 0.2 mg triptorelin (GnRH agonist (GnRHa)) as trigger were categorised in Group A (n = 129) and those who received 10,000 IU urinary hCG in Group B (n = 151). The outcome in terms of CPR was studied.Statistical Analysis Used:The quantitative variables were compared using the independent t-test/Mann–Whitney test. The qualitative variables were compared using the Chi-square test. P < 0.05 was considered statistically significant.Results:There was a trend toward better CPR in Group A (21/129 – 16.28%) than in Group B (16/151 – 10.60%), although the difference was not found to be statistically significant (P – 0.162).Conclusions:There was a trend toward better CPR with the use of GnRH agonist trigger in IUI cycles with oral ovulogens in comparison to hCG trigger, although the difference was not found to be statistically significant. Further randomized controlled trials are needed to confirm these findings.

Pre-Ovulatory Hormones on Day of Human Chorionic Gonadotropin Trigger and Assisted Reproductive Technique Outcomes in Different Ovarian Response Groups.

Background:Evidence regarding impact of pre-ovulatory hormone levels on assisted reproductive technique (ART) outcomes in different ovarian response groups is sparse.Aims:The objective of this study was to evaluate and compare the association between pre-ovulatory hormonal profile and ART outcomes in different ovarian responses.Setting and Design:This is a single-centre retrospective cohort study of 273 non-donor fresh ART cycles between January 2013 and June 2016.Materials and Methods:Data on clinical profile, basal and peak hormonal levels, characteristics of controlled ovarian stimulation and ART outcomes were collected. Progesterone elevation (PE) was defined as pre-ovulatory serum progesterone >1.5 ng/mL or progesterone to oestradiol ratio >1. The association between peak hormonal levels and ART outcomes in poor (≤4 oocytes retrieved), intermediate (5–13 oocytes retrieved) and high (≥14 oocytes retrieved) ovarian responders was analysed and compared.Statistical Analysis:Continuous and categorical variables were summarised as median (interquartile range) and percentages, respectively, and compared using Kruskal–Wallis H-test or Mann–Whitney U-test and Chi-square test or Fisher's exact test, respectively.Results:The incidence of PE, by both criteria and clinical pregnancy rates (35.7%, 36.8% and 18.6% in high, normal and poor responders, respectively; P = 0.073), was similar among the three response groups. Except fertilisation rates in normo-responders, PE did not influence ART outcomes in any response group. Furthermore, there were no differences between peak hormone concentrations or incidence of PE between those who conceived and those who did not.Conclusion:Pre-ovulatory sex steroid levels do not seem to be the primary determinant of ART outcomes in any ovarian response category; hence, decision to freeze all embryos in the event of PE should be tailored.

Optimal lead follicle size for human chorionic gonadotropin trigger in clomiphene citrate and intrauterine insemination cycles: an analysis of 1,676 treatment cycles

To identify the optimal lead follicle size for hCG trigger in clomiphene citrate (CC)-intrauterine insemination (IUI) cycles. Retrospective cohort study. University-affiliated center. Patients <40 years of age with ovulatory dysfunction or unexplained infertility undergoing their first CC-IUI cycle. Ovulation induction, hCG trigger, and IUI. Clinical pregnancy rate (CPR) was the primary outcome and was plotted against lead follicle size in increments of 1 mm. Odds ratios with 95% confidence intervals for associations between lead follicle size and CPR were calculated from a multivariable logistic regression model. A receiver operating characteristic (ROC) curve was generated for CPR as a function of lead follicle size. 1,676 cycles were included. The overall CPR was 13.8% (232/1,676). There was no difference in baseline demographics or ovulation induction parameters of patients who did or did not conceive. The odds of clinical pregnancy were 2.3 and 2.2 times higher with lead follicle sizes of 21.1-22.0 mm and >22.0 mm, respectively, compared with the referent category of 19.1-20.0 mm. Lead follicle size was an independent predictor of CPR, even after accounting for confounders. A lead follicle size of 22.1 mm corresponded to a sensitivity and specificity of 80.1% and 90.4% for clinical pregnancy, respectively, with an area under the ROC curve of 0.89. hCG administration at a lead follicle size of 21.1-22.0 mm is associated with higher odds of clinical pregnancy in patients undergoing their first CC-IUI cycles for ovulatory dysfunction or unexplained infertility.

Significance of endometrial thickness change after human chorionic gonadotrophin triggering in modified natural cycles for frozen-thawed embryo transfer.

BackgroundPeak endometrial thickness (EMT), measured on the end of follicular phase or early luteal phase, is the most widely used marker for endometrial receptivity during infertility treatment. However, the clinical significance of follicular-to-luteal EMT change remains unclear. We aimed to study whether the change of EMT between the day of human chorionic gonadotrophin (hCG) triggering and the day of frozen-thawed embryo transfer (FET) has any influence on pregnancy outcomes in modified natural cycles (mNCs).MethodsThis was a retrospective cohort study of 2,768 regular ovulatory women who underwent their first mNC-FET cycles from January 2011 to June 2015. Patients were divided into three groups according to the percentage change of EMT from the hCG triggering day to the FET day: >5% decrease (n=405), ±5% plateau (n=1,259) and >5% increase (n=1,104). The main outcome measure was live birth rate.ResultsLive birth rates were 41.9%, 39.8% [crude odds ratio (cOR) 0.91, 95% CI, 0.73–1.15) and 42.4% (cOR 1.02, 95% CI, 0.87–1.20) in the EMT plateau, decrease and increase groups, respectively (P=0.649). Multiple regression analysis did not alter the finding after controlling for a variety of confounders. Compared with the post-trigger EMT plateau group, the adjusted OR of live birth was 0.88 (95% CI, 0.69–1.12) in the decrease group and 1.05 (95% CI, 0.88–1.25) in the increase group. Similarly, no significant associations were observed before or after adjustment between EMT change and other pregnancy outcomes including positive hCG test, clinical pregnancy, early miscarriage and ongoing pregnancy.ConclusionsEMT change from hCG triggering to embryo transfer was not associated with pregnancy chances in mNC-FET cycles. This reassuring finding should provide guidance for physicians and patients when confronted with EMT decrease on the transfer day.

Triple stimulation (TriStim) before bilateral oophorectomy in a young woman with ovarian cancer: a case report and review of the literature

BackgroundDouble ovarian stimulation (DuoStim) involves two rounds of controlled ovarian stimulation (COS) and oocyte retrieval in immediate succession. It represents a promising approach to increase oocyte yield for patients with diminished ovarian reserve or those with limited time before fertility-threatening oncologic treatment. We report the case of a 31-year-old woman with Stage IC endometrioid ovarian cancer who underwent a triple stimulation or “TriStim,” completing three rounds of COS and oocyte retrieval within 42 days prior to bilateral salpingo-oophorectomy.Case presentationA 31 year old nulligravid woman presented for fertility preservation counseling following a bilateral ovarian cystectomy that revealed Stage IC endometroid adenocarcinoma arising within endometrioid borderline tumors. The patient was counseled for bilateral salpingo-oophorectomy, lymph node dissection, and omentectomy followed by three cycles of carboplatin/paclitaxel. Prior to this, all within six weeks, the patient underwent three rounds of controlled ovarian stimulation using an antagonist protocol and human chorionic gonadotropin (hCG) trigger, resulting in vitrification of nine two-pronuclear zygotes (2PN), after which definitive surgery was performed.ConclusionsAdvantages of DuoStim procedures are increasingly recognized, especially for oncology patients with limited time before potentially sterilizing cancer treatment. To our knowledge, this is the first report of a triple stimulation (“TriStim”). Our case highlights that triple stimulation is a viable option for patients needing urgent fertility preservation in order to maximize egg and embryo yield within a limited time period.

Comparison of oocyte maturity rates in recombinant Human Chorionic Gonadotropin (HCG) and triptorelin acetate triggers: A prospective randomized study

Luteinizing Hormone (LH) like exposure in the mid cycle for inducing the oocyte maturation is the very crucial step in the success of ICSI treatment. Introduction of LH surge endogenously by GnRH-agonist for final oocyte maturation induction, may be more physiological compared with the administration of HCG. Since GnRH agonist would induce FSH surge also along with LH surge, as happens in natural cycle. However, the effects of giving HCG trigger for inducing only LH surge and giving GnRH agonist trigger for inducing both LH and FSH surge, in patients treated for ICSI with GnRH antagonists need more research. Sub fertile patients planned for ICSI, meeting the requirement of inclusion criteria, were started with recombinant FSH from day 2 of menstrual cycle. GnRH antagonists were started from day 6 of stimulation. FSH dose was adjusted according to the individual response. Trigger was planned when the lead follicle reaches 24 mm. For triggering, 100 patients were randomized to receive Recombinant HCG trigger and Triptorelin acetate trigger. Oocyte retrieval was done 36 hours after Recombinant hCG Trigger and 35 hours after Triptorelin acetate trigger. The oocyte maturity rate was assessed by the number of metaphase II oocytes retrieved.

A matched propensity score study of embryo morphokinetics following gonadotropin-releasing hormone agonist versus human chorionic gonadotropin trigger.

To compare morphokinetic parameters and quality of embryos derived from GnRH antagonist ICSI cycles triggered either with GnRH agonist or standard hCG between matched groups of patients. Morphokinetic parameters of embryos derived from matched first GnRH antagonist ICSI cycles triggered by GnRH agonist or standard hCG between 2013 and 2016 were compared. Matching was performed for maternal age, peak estradiol levels, and number of oocytes retrieved. Outcome measures were: time to pronucleus fading (tPNf), cleavage timings (t2-t8), synchrony of the second and third cycles (S2 and S3), duration of the second and third cycle (CC2 and CC3), optimal cell cycle division parameters, and known implantation data (KID) scoring for embryo quality. Multivariate linear and logistic regression analyses were performed for confounding factors. We analyzed 824 embryos from 84 GnRH agonist trigger cycles and 746 embryos from 84 matched hCG trigger cycles. Embryos derived from the cycles triggered with hCG triggering cleaved faster than those deriving from GnRH agonist trigger. The differences were significant throughout most stages of embryo development (t3-t6), and a shorter second cell cycle duration of the hCG trigger embryos was observed. There was no difference in synchrony of the second and third cell cycles and the optimal cell cycle division parameters between the two groups, but there was a higher percentage of embryos without multinucleation in the hCG trigger group (27.8% vs. 21.6%, p < 0.001). The type of trigger in matched antagonist ICSI cycles was found to affect early embryo cleavage times but not embryo quality.

Early Progesterone Change Associated With Pregnancy Outcome After Fresh Embryo Transfer in Assisted Reproduction Technology Cycles With Progesterone Level of >1.5 ng/ml on Human Chorionic Gonadotropin Trigger Day.

Several studies have reported a poor implantation rate for assisted reproduction technology (ART) cycles with elevated progesterone (P4) at the end of the follicular phase. Whether all women with increased P4 on the human chorionic gonadotropin(hCG) trigger day should undergo fresh or frozen embryo transfer (ET) remains to be explored. This study attempted to determine that the P4 level on 2 days before hCG administration and P4 ratio can serve as indicators for fresh ET in normal responders with an elevated P4 level of >1.5 ng/ml on the hCG administration day. This was a retrospective cohort study involving 337 ART cycles with fresh ET for normal responders. Serum P4 levels were measured 2 days prior to hCG day (P4 level I) and on the hCG administration day (P4 level II). The P4 ratio was calculated as follows: P4 ratio = P4 level II / P4 level I. The primary outcome is live birth rate of fresh ET cycles. The ROC curves established that the optimal P4 level I and P4 ratio for pregnancy in ART cycles with high P4 level II were 0.975 ng/ml and 1.62, respectively. Patients with a P4 level I of ≤0.975 ng/ml and P4 ratio of >1.62 were associated with a significantly higher implantation (30.8%, 61/198 vs. 10.3%, 19/184, p < 0.001) and live birth rates (51.6%, 33/64 vs. 15.0%, 9/60, p < 0.001) compared with those with a P4 level I of >0.975 ng/ml and P4 ratio of ≤1.62. A combination of P4 level I and P4 ratio cutoff values of 0.975 ng/ml and 1.62, respectively, had a positive predictive value (PPV) of 82.5% for pregnancy. In conclusion, fresh ET can be an option for women with an early P4 level I under 0.975 ng/ml and a P4 ratio higher than 1.62, especially for those normal responders with an elevated P4 level II >1.5 ng/ml on the hCG administration day. This approach may shorten the time to pregnancy and reduce the cost of ART cycles.

RELATIONSHIP BETWEEN TEMPORAL CHANGES OF ENDOMETRIAL BLOOD FLOW IMPEDANCE IN A NATURAL AND HORMONE REPLACEMENT CYCLE AND PREDICTION OF PREGNANCY DURING VITRIFIED-WARMED EMBRYO TRANSFER

Frozen-thawed embryo transfer (ET) is performed in a natural or hormone replacement therapy (HRT) cycle for endometrial preparations. However, how to determine which endometrial preparation method is suitable for the individual is unknown.This study was to examine the relationship between the temporal changes in endometrial blood flow impedance during natural and HRT cycles and clinical outcomes in vitrified-warmed ET. A single-center retrospective observational cohort study. This study was approved by the institutional review board of the Fukushima Medical University. This study included a total of 60 women, 28 with natural and 32 with HRT cycles, who underwent vitrified-warmed ET. Uterine radial artery resistance index (RA-RI) was measured during the natural and HRT cycles at the early follicular phase, days of the human chorionic gonadotropin trigger during a natural cycle or start of progesterone administration during the HRT cycle, and the day of ET. The association between the RA-RI at the different measurement point and the pregnancy were examined in the natural and HRT cycles by univariate analysis and multivariate logistic analysis. Receiver-operating characteristic analysis was used to determine the cut-off value of the RI with respect to pregnancy in natural and HRT cycles. The area under the curves (AUC) and their 95% confidence intervals (CI) were calculated. The clinical pregnancy rates of the natural and HRT cycles were 32.1% and 34.4%, respectively. In the univariate analysis, the RA-RI at the early follicular phase was significantly lower in the pregnant group than that in the non-pregnant group in the natural but not HRT cycle (P=0.04). In the multivariate logistic analysis, the RA-RI at the early follicular phase was an independent predictive factor for pregnancy in the natural but not HRT cycle (P=0.02). The odds ratio for pregnancy was 0.7 (95% CI, 0.52–0.95) when the levels of RA-RI at the early follicular phase was increased by 0.01 in the natural cycle. With the natural cycle, the area under the receiver-operating characteristic curves for the RA-RI at the early follicular phase with a threshold of 0.68 was 0.75 (95% CI, 0.57–0.93). The positive predictive and negative predictive values were 0.53 (95% CI, 0.37–0.59) and 0.92 (0.74–0.99), respectively. With the natural cycle, the RA-RI at the early follicular phase was associated with pregnancy, and this might have a potential in predicting pregnancy in vitrified-warmed ET cycles. Our findings suggest that RA-RI at the early follicular phase might be an effective and useful tool in choosing natural or HRT cycles for vitrified-warmed ET. This provides a clue to the individualization of the choice of an endometrial preparation method during the frozen-thawed ET.

Further evidence that a supraphysiologic estradiol level during ovarian stimulation affects birthweight: findings of fresh and frozen embryo transfer with comparable estradiol levels on human chorionic gonadotropin trigger

Studies have reported a supraphysiologic estradiol (E2) level during ovarian stimulation may be related to low birthweight after fresh embryo transfer (ET), but whether a high E2 level in the stimulation cycle affects birthweight via frozen ET remained controversial. The study was to investigate whether a supraphysiologic E2 level in ovarian stimulation cycle affects birth weight in infants conceived via subsequent FET. In this retrospective cohort study, 2525 singletons conceived via FET and 2668 singletons conceived via fresh ET were analyzed. The birthweight and incidences of small for gestational age (SGA) in infants conceived via FET in groups with low and high levels of E2 did not differ significantly. Multivariate analyses showed that the peak E2 level was not predictive of SGA in infants conceived via FET. Singletons conceived via fresh ET had a higher risk of SGA than those conceived via FET even after comparable previous exposure to a high level of E2 > 3000 pg/mL. Our study results indicated that the increased risk of SGA was at least partly a result of the supraphysiologic E2 exposure to the intrauterine environment.

Serum Progesterone Level in Agonist and Antagonist Protocols on the Day of Human Chorionic Gonadotropin Triggering in Prediction of Intracytoplasmic Sperm Injection Outcome

Background:The potential association of serum progesterone on the day of human chorionic gonadotropin administration with the outcome of intracytoplasmic sperm injection [ICSI] cycles has been one of the major controversies in the endocrinology of ovarian stimulation. Aim of the work: This study was conducted to estimate the net effect of progesterone elevation on the day of human chorionic gonadotrophin [hCG] on pregnancy outcome in women undergoing fresh embryo transfer in control ovarian stimulation using long agonist and antagonist protocols. Patients and Methods:This is a prospective study included a total of 177 patients who were indicated for ICSI. The included cases were divided into three groups according to progesterone level at the day of hCG. Both progesterone and E2 were estimated at the day of triggering. Results:Serum progesterone levels did not differ between cases who got pregnancy and who did not (p=0.435). Estrogen/Progesterone ratio was not significantly different between pregnant and non-pregnant females (p= 0.842). Conclusion: Progesterone level on the day of hCG administration does not have any effect on ICSI outcome.

Do spontaneously decreasing estradiol levels prior to triggering of ovulation adversely impact in vitro fertilization outcomes?

ObjectiveThe aim of this study was to explore the potential adverse effect of spontaneously decreasing serum estradiol (SE) levels on in vitro fertilization (IVF) outcomes.MethodsThis retrospective single-subject study analyzed IVF cycles conducted at a hospital IVF unit between 2010 and 2017. Overall, 2,417 cycles were analyzed. Only cycles with spontaneously decreasing SE before human chorionic gonadotropin (hCG) triggering were included. Each patient served as her own control, and subsequent cycles were analyzed for recurrent SE decreases. The main outcome was the number of oocytes retrieved.ResultsCycle characteristics were similar between the study (SE decrease) and control groups, with the exception of the median SE on the day of hCG triggering (899.7 pg/mL; interquartile range [IQR], 193–2,116 pg/mL vs. 1,566.8 pg/mL; IQR, 249–2,970 pg/mL; p < 0.001). The study group, relative to the control group, had significantly fewer total oocytes (5 [IQR, 2–9] vs. 7 [IQR, 3–11]; p = 0.002) and significantly fewer metaphase II (MII) oocytes (3 [IQR, 1–6] vs. 4 [IQR, 2–8]; p = 0.001) retrieved. The study group had fewer cleavage-stage embryos than the control cycles (3 [IQR, 1–6] vs. 4 [IQR, 2–7]; p = 0.012). Compared to cycles with a ≤ 20% SE decrease, cycles with a > 20% decrease had significantly fewer total and MII oocytes retrieved. SE decrease recurred in 12% of patients.ConclusionA spontaneous decrease in SE levels adversely affected IVF outcomes, with a linear correlation between the percentage decrease and the number of oocytes retrieved. SE decrease can repeat in later cycles.

Bypassing physiological puberty, a novel procedure of oocyte cryopreservation at age 7: a case report and review of the literature

To report the first successful oocyte cryopreservation in a prepubertal girl. Case report and review of the literature. Tertiary medical center. A 7-year-old prepubertal girl with Turner syndrome mosaicism (45,X[37]/47,XXX[15]) who underwent a novel fertility preservation procedure after fertility preservation counseling and informed decision of the parents. Controlled ovarian hyperstimulation with daily administration of 100 IU recombinant human follicle-stimulating and 50 IU recombinant human luteinizing hormone per milliliter, injection of 250 μg human chorionic gonadotropin was given 36 hours before the follicular aspiration procedure, and oocytes retrieved by a transabdominal ultrasound guided approach. Mature oocyte cryopreservation. The first cryopreservation cycle with use of a gonadotropin-releasing hormone agonist trigger failed to yield oocytes. The second cycle with human chorionic gonadotropin trigger was successful. Six oocytes were retrieved, and all were mature metaphase 2. The patient was discharged in good condition with no complications. This novel procedure bypasses the timely physiologic progression of pubertal maturation of the hypothalamic-pituitary-ovarian axis to directly target the ovaries and achieve mature ovarian follicles. This innovative approach offers a new treatment modality for prepubertal girls who need fertility preservation such as in Turner syndrome or in cases that ovarian tissue cryopreservation is contraindicated.

Superovulation with human chorionic gonadotropin (hCG) trigger and gonadotropin releasing hormone agonist (GnRHa) trigger differentially alter essential angiogenic factors in the endometrium in a mouse ART model†.

Gonadotropin-releasing hormone agonists (GnRHa) are used as an alternative to human chorionic gonadotropin (hCG) to trigger ovulation and decrease the risk of ovarian hyperstimulation syndrome. GnRHa is less potent at inducing ovarian vascular endothelial growth factor (VEGF), but may also affect endometrial angiogenesis and early placental development. In this study, we explore the effect of superovulation on endometrial angiogenesis during critical periods of gestation in a mouse model. We assigned female mice to three groups: natural mating or mating following injection with equine chorionic gonadotropin and trigger with GnRHa or hCG trigger. Females were killed prior to implantation (E3.5), post-implantation (E7.5), and at midgestation (E10.5), and maternal serum, uterus, and ovaries were collected. During peri-implantation, endometrial Vegfr1 and Vegfr2 mRNA were significantly increased in the GnRHa trigger group (P<0.02) relative to the hCG group. Vegfr1 is highly expressed in the endometrial lining and secretory glands immediately prior to implantation. At E7.5, the ectoplacental cone expression of Vegfa and its receptor, Vegfr2, was significantly higher in the hCG trigger group compared to the GnRHa group (P<0.05). Soluble VEGFR1 and free VEGFA were much higher in the serum of mice exposed to the hCG trigger compared to GnRHa group. At midgestation, there was significantly more local Vegfa expression in the placenta of mice triggered with hCG. GnRHa and hCG triggers differentially disrupt the endometrial expression of key angiogenic factors during critical periods of mouse gestation. These results may have significant implications for placental development and neonatal outcomes following human in vitro fertilization.

Rescue In Vitro Maturation in Polycystic Ovarian Syndrome Patients Undergoing In Vitro Fertilization Treatment who Overrespond or Underrespond to Ovarian Stimulation: Is It A Viable Option? A Case Series Study.

BackgroundThis study intends to present the role of rescue in vitro maturation (IVM) in polycystic ovarian syn- drome (PCOS) patients undergoing in vitro fertilization (IVF) treatment who have inappropriate responses to ovarian stimulation.Materials and MethodsThis was a retrospective case series study of five PCOS patients undergoing IVF treatment considered for cycle cancellation due to increased risk of ovarian hyperstimulation syndrome (OHSS) as group A or poor response to ovarian stimulation as group B. Patients in group A had high oestradiol levels and recruitment of high numbers of small/intermediate sized follicles that did not meet the criteria for human chorionic gonadotropin (hCG) triggering. Patients in group B responded inadequately to hormonal stimulation despite high gonadotropin dosage. Treatment was changed to rescue IVM cycles after the patients provided consent.ResultsIn group A, three IVF patients deemed to have high chances of developing OHSS as evidenced by high oestradiol levels were converted to IVM. A total of the 58/68 oocytes retrieved were mature or matured in vitro. There were 26 cleaving embryos obtained. Two patients had live births and one patient suffered a miscarriage. In group B, rescue IVM was implemented in two patients due to poor ovarian response (POR). A total of 22/26 oocytes retrieved were mature or matured in vitro. There were 13 cleaving embryos obtained. One patient had a live birth, whilst the other suffered a miscarriage.ConclusionRescue IVM could be a viable option in PCOS patients undergoing IVF treatment who are unable to safely meet the criteria for hCG triggering due to overresponse to ovarian stimulation or ovarian resistance to high doses of stimulation. Conversion to IVM can still result in reasonable oocyte retrieval and lead to clinical pregnancy and live births without the risks of OHSS.

The Effect of Follicle-Stimulating Hormone Administration on the Day of Human Chorionic Gonadotropin Trigger on Assisted Reproductive Technique Outcomes in Patients Undergoing In vitro Fertilization-Embryo Transfer: A Retrospective Cohort Study.

Aim:The aim is to study the effect of follicle-stimulating hormone (FSH) administration on the day of human chorionic gonadotropin (hCG) trigger on the assisted reproductive technique (ART) outcomes in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles.Settings and Design:Retrospective cohort study was conducted in the ART center of our hospital.Materials and Methods:Two hundred and ninety IVF/ICSI cycles performed between September 2012 and August 2017 were included in the study. Patients who received 375 IU of FSH on the day of hCG trigger (149 cycles) were compared with those who did not receive FSH on the day of trigger (141 cycles).Statistical Analysis Used:Chi-square test and Student's t-test were used.Results:The FSH co-administered group had a significantly higher number of oocytes retrieved, mature oocytes, and fertilization rate compared to those who did not receive FSH on the day of trigger (p < 0.001). The total number of embryos, the number of grade 1 embryos and the number of embryos available for cryopreservation were also significantly higher in the FSH administered group (p < 0.001). Implantation rate, clinical pregnancy rate, and live birth rate were not significantly different between the two groups.Conclusions:This study has shown that FSH administration on the day of the trigger may be considered in IVF cycles receiving hCG trigger to improve the oocyte recovery and maturity if the patient is not at increased risk of ovarian hyperstimulation and serum estradiol on the day of the trigger is <4500 pg/ml. However, there is only an increase in the total number of oocytes retrieved and the number of mature oocytes but no significant change in the implantation, clinical pregnancy, and live birth rates.

Preparation of the endometrium and timing of blastocyst transfer in modified natural cycle frozen-thawed embryo transfers (mNC-FET): a study protocol for a randomised controlled multicentre trial

IntroductionDespite the high number of frozen embryo transfer (FET) cycles being conducted (190 000 cycles/year) in Europe, the timing of blastocyst transfer and the use of luteal phase progesterone support...

Oocyte exposure to supraphysiological estradiol during ovarian stimulation increased the risk of adverse perinatal outcomes after frozen-thawed embryo transfer: a retrospective cohort study.

Maternal supraphysiological estradiol (E2) environment during pregnancy leads to adverse perinatal outcomes. However, the influence of oocyte exposure to high E2 levels on perinatal outcomes remains unknown. Thus, a retrospective cohort study was conducted to explore the effect of high E2 level induced by controlled ovarian stimulation (COH) on further outcomes after frozen embryo transfer (FET). The study included all FET cycles (n = 10,581) between 2014 and 2017. All cycles were categorized into three groups according to the E2 level on the day of the human Chorionic Gonadotropin trigger. Odds ratios (ORs) and their confidence intervals (CIs) were calculated to evaluate the association between E2 level during COH and pregnancy outcomes and subsequent neonatal outcomes. From our findings, higher E2 level was associated with lower percentage of chemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth as well as increased frequency of early miscarriage. Preterm births were more common among singletons in women with higher E2 level during COH (aOR1 = 1.93, 95% CI: 1.22-3.06; aOR2 = 2.05, 95% CI: 1.33-3.06). Incidence of small for gestational age (SGA) was more common in both singletons (aOR1 = 2.01, 95% CI: 1.30-3.11; aOR2 = 2.51, 95% CI: 1.69-3.74) and multiples (aOR1 = 1.58, 95% CI: 1.03-2.45; aOR2 = 1.99, 95% CI: 1.05-3.84) among women with relatively higher E2 level. No association was found between high E2 level during COH and the percentage of macrosomia or large for gestational age. In summary, oocyte exposure to high E2 level during COH should be brought to our attention, since the pregnancy rate decreasing and the risk of preterm birth and SGA increasing following FET.