Day Of hCG Trigger Research Articles

Impact of Serum Progesterone Levels in GnRH Antagonist Assisted Reproduction Cycles on Pregnancy Outcomes: A Prospective Cohort Study

Background: With controlled ovarian hyperstimulation (COH) with gonadotrophin releasing hormone (GnRH) antagonists, sometimes it is associated with incomplete luteolysis leading to elevated serum progesterone in early follicular phase. Persistence of this elevation might reduce the chance for clinical pregnancy. Objective: To assess the effect of elevated early and late follicular progesterone (P) levels during gonadotrophins releasing hormone (GnRH) antagonist cycles on pregnancy outcome. Design: Prospective single center study. Setting: North-western Military hospital, Kingdom of Saudi Arabia. Patients: 302 in vitro fertilization/intra-cytoplasmic sperm injection (IVF-ICSI) patients. Intervention(s): Recombinant follicle stimulating hormone (r-FSH), (150 - 300 IU) started daily from cycle day 2; GnRH antagonist treatment started on day 6 of the cycle. The serum progesterone (P) measured twice on cycle day 2 and human chorionic gonadotrophin (hCG) day. Main Outcome Measures: Clinical pregnancy and live birth rates per started cycle. Results: The incidence of elevated serum P on day 2 was (5.3%) and on hCG day was (17.5%), statistically significant differences in clinical pregnancy rate (32.3% versus 13.0%) and in live birth rate (23.4% versus 11.1%) were present between the normal and high serum progesterone groups on hCG day, but these differences were not statistically significant in the groups of elevated basal progesterone. Conclusion: Follicular phase progesterone rise either on day 2 or the day of hCG trigger was associated with lower clinical pregnancy and live birth rates. This impact was more prominent with trigger day elevation.

Evaluating the benefit of measuring serum progesterone prior to the administration of HCG: effect of the duration of late-follicular elevated progesterone following ovarian stimulation on fresh embryo transfer live birth rates.

Progesterone overproduction during ovarian stimulation is associated with lower live birth rates (LBR) after fresh embryo transfer. Therefore, circulating P concentrations on the day of HCG administration are frequently measured in clinical practice and followed by an elective cryopreservation strategy whenever late-follicular elevated P (LFEP) occurs. A recent study concluded that the duration of LFEP >1.00 ng/mL prior to HCG administration may also affect clinical pregnancy rates. The objective of this current study was to assess whether this hypothesis was reproducible using LBR as the primary outcome. Retrospective analysis including women undergoing IVF/ICSI between 2010-2015. LBR were compared among different P elevation duration subgroups (0, 1 or >1 day) using two LFEP thresholds (>1.00 ng/mL and >1.50 ng/mL). The duration of LFEP >1.00 ng/mL was not associated with a significant decrease in LBR according to whether the patient had LFEP lasting for 0, 1 or >1 days (29.9%, 30.3% and 26.3%, respectively). Conversely, when using >1.50 ng/mL as the LFEP threshold, LBR decreased significantly (30.3% 20.4% and 20.5%, respectively). However, the relative frequency of having LFEP >1.50 ng/mL for >1 day was exceedingly rare (1.9%) and the additional benefit of evaluating LFEP beyond the day of HCG triggering no longer remained statistically significant after confounder-adjustment with multivariable regression analysis. These results suggest a lack of benefit in measuring serum P in the days preceding HCG administration, since LBR in women with LFEP >1 day do not vary significantly from those with LFEP detected only on the day of HCG administration.

The effect of estradiol valerate with and without oral sildenafil on endometrial thickness and pregnancy rates in infertile women: A R.C.T

Objective: Clomiphene citrate (CC) has some negative effects on the endometrium. We evaluated the effect of concomitant administration of oral sildenafil and estrogen on endometrial thickness (ET), pattern and pregnancy rates in CC stimulated cycles in infertile women diagnosed as unexplained infertility. Aim of the Work: Compare the effect of sildenafil‌-estrogen combination to estrogen alone on endometrium thickness in infertile women. Materials and methods: It is a randomized controlled trial on 90 infertile women with unexplained infertility; patients were randomly divided into two equal groups. In control group, 45 patients were given ovulation induction with CC 100mg/d from 2nd to 6th day of cycle and oral estradiol valerate 2mg 12 hourly from 2nd day of the cycle till the day of trigger of ovulation. In study group, 45 patients were given ovulation induction with CC100mg/d from 2nd to 6th day of cycle, estradiol valerate 2mg 12 hourly plus oral sildenafil citrate 25mg every 8 h from 2nd day of the cycle till the day of hCG trigger. A transvaginal ultrasound was performed on day 10 to assess follicular growth until the detection of at least one dominant follicle ≥18 mm. At that time, the endometrium was evaluated as regards both endometrial thickness and pattern. Uterine artery resistive index (RI) was then measured. Qualitative serum B-hCG level was checked 14 days after ovulation to assess chemical pregnancy rate. Results: Mean endometrial thickness at the time of hCG trigger was 9.8 mm in study group and 8.42 mm in control group (p value <0.001). 88.9% patients given sildenafil had trilaminar endometrium whereas 29% patients without sildenafil had trilaminar endometrial pattern (p value = 0.006). Mean uterine artery resistive index (RI) after adding sildenafil was non-significantly lower among study group than among control group; the values were 0.66 and 0.72, respectively (P= 0.078). Pregnancy rates in study group and control group were 17.8% and 11.1%, respectively. Conclusion: Sildenafil‌-estrogen combination has a potent effect on improving the endometrium (thickness and pattern) in patients undergoing induction of ovulation by clomiphene citrate. This improvement in endometrial development has a weak positive feedback on pregnancy rate.

Does the addition of a GnRH antagonist on day of HCG trigger in couples undergoing an antagonist protocol for in vitro fertilization (IVF) increase total oocyte yield?

Does the addition of a GnRH antagonist on day of HCG trigger in couples undergoing an antagonist protocol for in vitro fertilization (IVF) increase total oocyte yield?

High serum estradiol level on the day of HCG trigger is associated with small for gestational age infants: a retrospective cohort study

High serum estradiol level on the day of HCG trigger is associated with small for gestational age infants: a retrospective cohort study

Endometrial thickness of less than 7.5 mm is associated with obstetric complications in fresh IVF cycles: a retrospective cohort study.

Does endometrial thickness affect the occurrence of obstetric complications in fresh IVF cycles? We conducted a retrospective cohort study that included all singleton deliveries resulting from fresh embryo transfers in a single centre between 2008 and 2014. Obstetric complications, i.e. preeclampsia, placental abruption, placenta previa, small for gestational age and preterm delivery, in singleton live births were compared among patients with an endometrial thickness of less than 7.5 mm and 7.5 mm or over on day of HCG triggering. We adjusted for confounders, including maternal age, body mass index, smoking, peak oestradiol, parity, chronic hypertension, pre-gestational diabetes, gestational diabetes, vanishing twin, inherited or acquired thrombophilia, and past pregnancy complications. A total of 5546 fresh embryo transfer cycles were carried out during the study period, of which 864 singleton deliveries met inclusion criteria. After adjusting for potential confounders, an endometrial thickness of less than 7.5 mm was found to be associated with increased risk for adverse obstetric outcome (adjusted OR 1.53; 95% CI 1.03 to 2.42; P = 0.04) even after excluding patients with prior pregnancy complications (adjusted OR 2.2; 95% CI 1.05 to 4.59; P = 0.035). Our results demonstrated that a thin endometrial lining was associated with obstetric complications that might be related to poor placentation. These findings should be validated in large prospective cohort studies.

The impact of endometrial thickness (EMT) on the day of human chorionic gonadotropin (hCG) administration on pregnancy outcomes: a 5-year retrospective cohort analysis in Malaysia

BackgroundChances of pregnancy in relation to endometrial thickness (EMT) remain elusive albeit some literatures suggest poorer pregnancy outcomes below the threshold of 6-7 mm, notwithstanding others perceive detrimental effect at thicker EMT. We aim to examine the implication of EMT on pregnancy outcomes using a cut-off of 8 mm and further explore for any effect of ‘thick’ EMT in our patient population.MethodsThis was a retrospective cohort study performed for 162 women to assess the associations between EMT on the human chorionic ganadotropin (hCG) trigger day and pregnancy outcomes in infertile patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) and autologous fresh embryo transfer (ET) in controlled ovarian stimulation (COS) cycles under an assisted reproductive technology (ART) shared-care programme between public and private institutions from January 2012 through December 2016.The associations between pregnancy outcomes [Total Pregnancy Rate (TPR), Biochemical Pregnancy Rate (BPR), Clinical Pregnancy Rate (CPR), Ongoing Pregnancy Rate (OPR)/ Live Birth Delivery Rate (LBDR), Miscarriage Rate (MR) and Implantation Rate (IR)] and EMT (< 8 or ≥ 8 mm) on the hCG trigger day were evaluated. Besides, the associations between pregnancies outcomes with EMT ≥ 14 mm and ≥ 8 to < 14 mm were further assessed.ResultsWe found that the ≥8 mm group had a higher TPR (55.4% vs 21.4%; p = 0.015) and CPR (52.0% vs 21.4%; p = 0.029). However, the BPR, MR, OPR/ LBDR and IR were not associated with the EMT (p > 0.05). All pregnancy outcomes were comparable for ≥14 mm and ≥ 8 to < 14 mm subgroups.ConclusionsOur findings suggest that EMT < 8 mm on hCG trigger day could adversely affect TPR and CPR in infertile patients undergoing IVF/ICSI-ET. Besides, we also disprove the notion of reduced chances of pregnancy with EMT ≥ 14 mm. The findings are based on completed cycles which each has demonstrated a triple-line endometrial pattern on the hCG trigger day with fresh autologous ET consisted of high-quality morphological gradings. However, our findings are still preliminary to suggest decision for ET transfer, cycle cancellation or adjunctive therapies. Further studies with larger sample size from this geographical region are required to verify the findings.

Effects of oestradiol for luteal phase support in fresh embryo transfer cycles: A retrospective cohort study.

Any benefit of oestradiol supplementation with progesterone for luteal support after fresh embryo transfer in in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) cycles remains controversial. In this study, we further addressed this question in cycles using gonadotropin-releasing hormone (GnRH) agonist for ovarian stimulation. A retrospective cohort study in a tertiary teaching and research hospital. A total of 1602 patients were given oestradiol valerate (E) in addition to progesterone (P) as luteal support. One thousand six hundred and two patients receiving progesterone alone were selected as the control group. Live birth rate. Secondary measures included clinical pregnancy rate, miscarriage rate and premature birth rate. Clinical pregnancy and live birth rates were similar for the P alone vs the P+E group. In cycles with oestradiol (E2) levels less than 5000pmol/L on the day of hCG trigger, E supplementation resulted in a significantly higher live birth rate (23.44% vs 32.92%, OR=1.60 [95% CI 1.05 to 2.46]). In cycles with oestradiol levels 5000 to 10000pmol/L on the day of hCG trigger, E supplementation did not increase the live birth rate (34.43% vs 35.42%, OR=0.90 [95% CI 0.80 to 1.01]). In cycles with oestradiol levels over 10000pmol/L on the day of hCG trigger, the live birth rate was significantly lower (36.83% vs 31.37%, OR=0.78 [95% CI 0.62 to 0.99]) and the premature birth rate was significantly higher (19.66% vs 28.73%,OR=1.65 [95% CI 1.05 to 2.59]) in the E supplementation group. Any benefit of oestradiol supplementation for luteal phase support appears to correlate with the serum oestradiol level on the day of hCG trigger. Oestradiol supplementation is beneficial for improving live birth rate in cycles with oestradiol levels less than 5000pmol/L, but is not recommended in cycles with oestradiol levels over 10000pmol/L.

Gonadotropin-releasing hormone receptor antibody activity over time in women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a diagnosis of exclusion with unknown etiology. We recently identified autoantibodies (AAbs) to the second extracellular loop (ECL-2) of the gonadotropin releasing hormone receptor (GnRHR) in a majority of patients with PCOS compared to ovulatory controls in baseline serum measurements. The present assay may represent the desired serological test needed to effectively screen subjects for possible PCOS. Currently, no data exists regarding autoantibody activity over time or with changes in the hormonal milieu associated with infertility treatments, specifically controlled ovarian hyperstimulation (COH) with in vitro fertilization (IVF). To evaluate the levels of AAbs to GnRHR in the serum of eleven subjects with PCOS and infertility over time and observe for changes relative to hormonal fluctuations occurring over the course of infertility treatment. Sera samples from eleven women with PCOS and infertility drawn over multiple time points (0: not on medications, 1: down-regulation phase of an IVF cycle (oral contraceptives or lupron), 2: IVF stimulation day five, 3: day of hCG trigger, and 4: day of pregnancy test) during infertility treatments were assessed for GnRHR-AAbs. The de-identified samples were screened by ELISA for GnRHR-AAbs using a synthetic 28-mer peptide (LifeTein, Somerset, NJ) from the ECL2 of human GnRHR as coating antigen. Optical density (OD) values were read at 405 nm at 60 minutes. Covariates evaluated include age, body mass index (BMI), anti-Mullerian hormone (AMH) level, antral follicle count (AFC), IVF protocol (GnRH antagonist or agonist), estradiol level, and hormonal down-regulation during IVF preparation. Statistical analyses were performed using generalized estimating equations within a generalized linear modeling framework to account for the repeated measures within each patient. AAb levels did not differ significantly by patient age (range 25-40 years; p=0.85) or BMI (range 19.3-41.8; p=0.89). After taking into account inter-patient variation and inter-time point variation, there was an association between GnRHR-AAb levels and estradiol levels (higher AAb level with lower estradiol; p<0.0001). Also, the GnRH antagonist protocol was associated with lower AAb levels (p=0.019). Most inter-patient variation could not be attributed to any of the patient characteristics. However, after taking into account inter-time point variation only, inter-patient variation in AAb levels was partially attributable to an interaction between BMI and AMH (p<0.0001) but not to age (p=0.70) or AFC (p=0.97). There was significant intra-patient variation in AAb levels at both baseline (time point 0, not on meds, p=0.042) and during the down-regulation phase (time point 1, p<0.0001) that could not be attributed to any of the measured covariates. Our initial investigations have shown that most patients in our study with PCOS have activating AAbs to GnRHR compared to ovulatory controls. Our pilot study has demonstrated that there is inter-patient variation of GnRHR-AAb levels on no medications and while in the down-regulation phase in preparation for IVF. Additionally, the fluctuation in AAb levels with estradiol levels in GnRH antagonist protocol would suggest an association between the two clinical time points and potentially a relationship between estradiol and the GnRHR-AAbs.

Progesterone value on day of HCG trigger is not associated with outcomes from fresh embryo transfer

Progesterone value on day of HCG trigger is not associated with outcomes from fresh embryo transfer

The effect of follicular phase length on endometrial development and the outcomes of ovulation induction/intrauterine insemination (OI/IUI) cycles

Few, limited studies have reported that in IUI cycles a shorter follicular phase is associated with poorer pregnancy outcomes compared to a longer follicular phase [1,2]. However, these studies have been limited by small sample sizes and inadequate control of potential confounders. To evaluate the effect, if any, of follicular phase length on endometrial development and cycle outcomes among patients undergoing OI/IUI. Design: Retrospective cohort study Intervention: Data from 3404 IUI cycles derived from 1502 patients in which gonadotropins were used for OI were analyzed and stratified by follicular phase length (hCG trigger day ≤8 vs. >8). Outcome Measures: Primary outcomes included clinical pregnancy, multiple pregnancy, spontaneous abortion, and non-clinical pregnancy (ectopic/biochemical) rates (CPR, SABR, MPR, and non-CPR, respectively). A secondary outcome was endometrial thickness prior to hCG trigger. Statistics: Demographic factor comparisons between follicular phase length groups were analyzed with Student t-tests, Mann Whitney U-tests, and χ2- tests, as appropriate. Multilevel random and fixed effects regression models were used to calculate odds ratios (ORs) for pregnancy outcomes and regression coefficients for endometrial thickness first by comparing the follicular phase length groups (≤8 vs. >8 days), then by analyzing follicular phase length as a continuous variable. All models adjusted for potential confounders (age, BMI, day-3 FSH) determined a priori. Demographic and cycle characteristics of the study population, stratified by follicular phase length, are outlined in Table 1. After adjusting for potential confounders, cycles with a longer compared to those with a shorter follicular phase resulted in significantly higher CPR (14.0 vs. 9.0%, p = 0.02; respectively). The odds for clinical pregnancy (CP) were 38% higher in the former compared to the latter group, with the difference nearing significance (OR: 1.38, 95%CI: 0.96-1.99, p = 0.082). When follicular phase length was analyzed as a continuous variable, the odds of CP increased by 6.0% (95%CI: 3.0-10.0, p = 0.001) with each additional follicular phase day. Cycles with a longer compared to those with a shorter follicular phase had comparable SABR (21.0 vs. 17.0%, p = 0.54), MPR (11.0 vs. 9.0%, p = 0.58), and non-CPR (12.0 vs. 16.0%, p = 0.39). The former compared to the latter group had similar odds for SAB (OR 1.56, 95%CI: 0.68-3.58, p = 0.293), MP (OR 1.40, 95%CI: 0.47-4.15, p = 0.544), and non-CP (OR 0.66, 95%CI: 0.28-1.58, p = 0.355). Likewise, when analyzed as a continuous variable, follicular phase length did not significantly impact the odds for SAB (OR 1.07, 95%CI: 0.99-1.14, p = 0.07), MP (OR 1.01, 95%CI: 0.94-1.10, p = 0.743), or non-CP (OR 0.98, 95%CI: 0.90-1.07, p = 0.687). Endometrial thickness was increased in cycles with a longer compared to shorter follicular phase with an adjusted mean difference of 1.12 mm (95% CI: 0.93-1.31, p < 0.001). Furthermore, endometrial thickness increased by 0.12 mm (95% CI: 0.09-0.15, p <0.001) with each additional follicular phase day. In gonadotropin-induced IUI cycles, a longer follicular phase is associated with increased endometrial thickness and possibility of clinical pregnancy.

Serum progesterone concentrations before and after human chorionic gonadotropin triggering and invitro fertilization : Intracytoplasmic sperm injection cycle outcome in long gonadotrophin releasing hormone agonist protocol

Objective: To assess the impact of serum progesterone concentrations before and after HCG triggering on IVF/ICSIcycle outcomes in long GnRHa protocol.Patients and Methods: This is a single-center prospective observational cohort study, in which 102 IVF/ICSI patients with normal cycle day 2 basal hormones were recruited and underwent ovarian stimulation using the long GnRHa protocol. Serum progesterone on the day of HCG trigger; one day after, progesterone/estradiol was assessed and correlated with pregnancy rates, the total dose of used gonadotropins, serum estradiol level on day of trigger, the number of collected oocytes, the number of metaphase II oocytes and the quality of transferred embryos.Results: 96 women were included in the analysis. In our study, the receiver-operating characteristic (ROC) analysis was used to gain more diagnostic accuracy. Our data according to ROC analysis showed that the P levels on the day of hCG trigger, and its levels one day after and P/E2 on the day of hCG trigger had no role in prediction of clinical pregnancy rates. There was significant correlation between the serum progesterone levels before and after HCG triggering with the total dose of gonadotropins used. They also correlated strongly with serum estradiol level on day of trigger, the number of collected oocytes and the number of metaphase II oocytes.Conclusion: Peri-ovulatory serum progesterone concentrations cannot predict pregnancy rates in IVF/ICSI cycles using long GnRHa protocol.

Effect of the initiation of progesterone supplementation in in vitro fertilization–embryo transfer outcomes: a prospective randomized controlled trial

To analyze the influence of the start point of luteal support on clinical pregnancy rate, implantation rate, and live birth rate of invitro fertilization and embryo transfer (IVF-ET) cycles. Single-center prospective randomized controlled trial. University-affiliated IVF unit. Women ≤35years of age with day 3 FSH levels <15 mIU/mL, who were undergoing their first IVF-ET cycles and received ovarian stimulation with the use of a GnRH agonist long protocol. The patients were randomized on the day of hCG trigger to receive luteal phase support either 1day after oocyte retrieval (group A) or on the day of oocyte retrieval (group B). Clinical pregnancy rate, implantation rate, miscarriage rate in the first trimester of pregnancy, and live birth rate per embryo transfer cycle. Two hundred thirty-three patients were enrolled in this study: 117 were assigned to group A and 116 to group B. The clinical pregnancy rate (group A vs. group B: 55.3% vs. 51.5%), implantation rate (38.4% vs. 38.0%), and miscarriage rate (7.7% vs. 7.5%) were similar between the two groups. The live birth rate also did not significantly differ between the two groups (45.7% vs. 46.6%). Our study indicated that the initiation of progesterone supplementation 1day after oocyte retrieval did not decrease the clinical pregnancy rate, implantation rate, or live birth rate in women undergoing IVF-ET cycles with the use of the GnRH agonist long protocol. ChiCTR-IPR-14005293.

Chromosomal polymorphisms are independently associated with multinucleated embryo formation.

The purpose of this study is to explore the factors associated with embryo multinucleation, particularly focused on the influence of parental chromosomal polymorphisms in embryo multinucleation. This is a retrospective case-control study involving 1260 infertile couples undergoing their first IVF/ICSI cycles. Couples were screened for abnormalities in their karyotype and were evaluated for blastomere persistence of multinucleation. Demographic characteristics, stimulation protocol, and pregnant outcomes were analyzed using logistic regression analysis. The level of basal FSH was lower in the multinucleated embryos group (5.37 vs 5.72IU/L). The Multinucleated embryos group received less gonadotropins (1788.5 vs 1891.3IU), and the level of LH on day of HCG triggering was lower (1.09 vs 1.30IU/L). More oocytes were recovered in the multinucleated embryos group (11.51 vs 9.23). Chromosomal polymorphisms were seen in at least 1 out of 163 (12.9%) couples. Multivariate logistic regression analysis revealed that chromosomal polymorphisms were independently associated with an increase in the occurrence risk of multinucleated embryos (OR=1.61, 95% CI, 1.06-2.44) in the first IVF/ICSI cycle. The miscarriage rate in the multinucleated embryos group was 10% higher than that of the control group. Chromosomal polymorphisms were independently associated with multinucleation embryo formation. A higher LH level on the day of HCG triggering was associated with a decreased chance of multinucleation.

To flush or not to flush: a randomized controlled trial comparing follicular flushing and direct aspiration at oocyte retrieval in poor responders undergoing IVF

Oocyte retrieval is a crucial step determining the outcome of IVF cycles. While routine flushing of follicles is not recommended (1) , it may improve the yield of oocytes and hence embryos available for transfer in poor responders. The objective of this study was to assess any improvement in ART outcome among women with poor response to stimulation during an IVF cycle Randomized controlled trial Seventy women with poor response to controlled ovarian stimulation (defined as 3-5 dominant follicles on the day of hCG trigger) during the index cycle were randomized to follicular flushing (Group A) or direct aspiration without flushing (Group B) at the time of oocyte retrieval.Women with endometriosis and adenomyosis and those with < 3 dominant follicles on day of trigger were excluded from the study. The primary outcome was total number oocytes retrieved, pregnancy and live birth rates. Secondary outcomes were procedure and anaesthesia time, fertilization, cleavage and implantation rates. Of the 70 women 42 were defined poor responders (as per Bologna criteria) while 28 presented with unexpected poor response (tubal and unexplained with normal ovarian reserves). There were a significantly higher number of oocytes retrieved in flushing group in comparison to direct aspiration [5(0-7) vs 4 (0-7); p=0.035]. The number of fertilized oocytes and number of good grade embryos were significantly higher in the flushing group (Gp A) compared to direct aspiration (Gp B), however the fertilization and cleavage rates were similar between both groups (Table I). The implantation and clinical pregnancy rates were significantly higher in the flushing group. The live birth rates were non-significantly better with flushing the follicles. The oocyte retrieval procedure and anaesthesia time was significantly longer in the flushing group (Table I). Flushing of follicles at the time of oocyte retrieval was of benefit in women with poor response to COH in terms of higher number of oocyte recovery and therefore more number of embryos available for transfer. Even though the procedure and anaesthesia time is longer it is worth flushing follicles in women with poor response to COH for better live birth rates and significantly improved clinical pregnancy rates.

Elevated basal progesterone levels are associated with increased preovulatory progesterone rise but not with higher pregnancy rates in ICSI cycles with GnRH antagonists

ObjectiveTo ascertain the association between basal progesterone (P) levels and the occurrence of preovulatory progesterone rise (PPR) and clinical pregnancy rates (CPRs) in ICSI cycles with GnRH antagonists. Study designSerum P levels of 464 patients were measured on day 2 and day of hCG of cycles. Cycles with basal P levels>1.6ng/mL were cancelled. All embryos were cryopreserved in cycles with P levels≥2ng/mL on the day of hCG. The primary outcome measures were the incidence of PPR (P>1.5ng/mL) and CPR with regard to basal P. ResultsBasal P levels were significantly higher in cycles with PPR than in those without PPR (0.63±0.31 vs. 0.48±0.28ng/mL). Area under the curve for basal P according to ROC analysis to discriminate between elevated and normal P levels on the day of hCG was 0.65 (0.58–0.71 95% CI, p<0.01). The cut-off value for basal P levels that best discriminates between cycles with and without PPR was 0.65ng/mL. Cycles with basal P levels above 0.65ng/mL had a significantly higher incidence of PPR (30.9% vs. 13.5%) but similar clinical and cumulative pregnancy rates (38.8% vs. 31.1% and 41.7% vs. 32.6%, respectively) in comparison to cycles with basal P levels below 0.65ng/mL. In multivariate regression analysis, basal P levels, LH level on the first day of antagonist administration, and estradiol levels on the day of hCG trigger were the variables that predicted PPR. ConclusionBasal P levels were associated with increased incidence of PPR but not with CPR.

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

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

Endometrial thickness influences neonatal birth weight in pregnancies with obstetric complications achieved after fresh IVF–ICSI cycles

Pregnancy-associated complications, duration of gestation and parity are well-known predictors of neonatal birth weight. Assisted reproductive technology (ART) affects neonatal birth weight as well. Endometrial thickness as measured on the day of HCG triggering may therefore impact on the neonatal birth weight. The data of 764 singleton deliveries achieved after fresh transfer between November 1997 and 2014 were collected retrospectively with the intention to analyze the relationship of maternal and neonatal characteristics with endometrial thickness and the possible predictive value of endometrial thickness on neonatal birth weight. Higher maternal age (p<0.001), diminished ovarian reserve (p<0.001), endometriosis (p=0.008) and hypogonadotropic hypogonadism (p<0.001) predicted thin endometrium. Neonatal birth weight (p=0.004), longer duration of pregnancy (p=0.008), parity (p=0.026) and higher maternal BMI (p=0.003) were correlated significantly with the degree of endometrial proliferation. Endometrial thickness strongly predicted neonatal birth weight (p=0.004). After adjusting regression analysis for maternal age and BMI, parity, neonatal gender and pregnancy duration, endometrial thickness remained predictive for neonatal birth weight in pregnancies with obstetric complications (p=0.017). In uneventful pregnancies duration and parity are determinants of neonatal birth weight. Our findings suggest that endometrial thickness is an additional ART-related factor influencing neonatal birth weight. This finding should be confirmed in large cohort studies.

Comparison of GnRH antagonist and agonist mini-dose long protocols in infertile cases undergoing controlled ovarian hyperstimulation

The purpose of the present study was to determine if there is a difference between multi-dose gonadotropin releasing hormone (GnRH) antagonist protocol and long GnRH agonist protocol. This retrospective study compared the data pertaining to patients chosen as per predetermined acceptance criteria, 113 of whom were administered multi-dose antagonist protocol for controlled ovarian hyperstimulation (COH) while 133 were administered long agonist protocol for COH at Suleymaniye Teaching Hospital of Obstetrics and Gynecology. While cancellation rate was found to be significantly higher in antagonist group (17.7% vs 11.28%), the number of follicles > 14 mm and > 16 mm, E2 level, and the number of retrieved oocytes on the day of hCG trigger were significantly lower in the same group. However, there was no difference between fertilization rates and embryonic development rates. The pregnancy rates per transfer and per cycle were found to be 40.9% and 31.7%, respectively; in the antagonist group they were lower, though not significantly, when compared to agonist group (44.1% and 39.1%, respectively). Ongoing pregnancy rates were found to be similar between the groups. GnRH antagonist treatment protocol has a level of efficacy similar to agonist treatment protocol in terms of pregnancy results for all groups.

Recombinant LH supplementation in patients with a relative reduction in LH levels during IVF/ICSI cycles: A prospective randomized controlled trial

PurposeThe aim of this study was to assess the use of recombinant luteinizing hormone (rLH) supplementation in patients who experience a reduction in LH concentration during controlled ovarian hyperstimulation (COH) for IVF/ICSI. MethodsA multi-center prospective randomized controlled trial (RCT) was performed over three years. Two hundred and forty patients aged between 24 and 42 years undergoing IVF/ICSI treatment with a long down regulation (LDR) protocol were recruited. LH was measured on the day FSH was started and again 6days later. 100 patients had a 50% or greater reduction in LH levels and these were randomized to receive either recombinant LH (rLH) supplementation (group 1, n=43) or no additional rLH supplementation (group 2, n=57). Group 1 received rLH 75IU daily from day 7 of FSH stimulation to the day of HCG trigger. ResultsThere were no differences in either live birth or clinical pregnancy rates per embryo transfer between the two groups (27.8% vs. 37.0%, p=0.39, RR=0.75, 95%CI 0.39–1.44 and 36.1% vs. 43.5% p=0.51, RR=0.84, 95%CI 0.5–1.48, respectively). ConclusionIn conclusion the addition of rLH in patients with a relative reduction in serum LH concentration during COH for IVF/ICSI did not improve live birth or clinical pregnancy rates. However the results were not conclusive and further large well-designed RCTs are required to confirm these findings.