Does pituitary suppression affect live birth rate in women with congenital hypogonadotrophic hypogonadism undergoing intra-cytoplasmic sperm injection? A multicenter cohort study.

In this retrospective multicenter cohort study, women with congenital hypogonadotrophic hypogonadism (CHH) (n = 57) who underwent intra-cytoplasmic sperm injection in-between 2010-2014 were compared to age-matched controls with tubal factor infertility (n = 114) to assess ovarian stimulation cycle and pregnancy outcomes. Live birth rates (LBRs) per started cycle were 31.6 and 24.6% in CHH and controls groups, respectively (p = 0.36). Comparable success rates were also confirmed with the logistic regression analysis (OR: 1.44, 95% CI: 0.78-2.67, p = 0.24). Of the 57 women with CHH, 19 were stimulated with the gonadotropin-releasing hormone (GnRH) antagonist protocol, 13 with the long-GnRH-agonist protocol. Pituitary suppression (PS) was not employed in the remaining 25 cases. Compared to women with PS, women without PS had significantly higher embryo implantation rates (21.6 versus 52.6%, p = 0.03). Although there was a trend favoring no PS, LBRs (25.0 versus 40.0%, p = 0.26) per cycle were short of statistical significance. LBRs per cycle (57.1 versus 31.2%, p = 0.11) and miscarriage rates (11.1 versus 16.7%, p = 0.75) were similar between CHH women who were given estrogen + progesterone and progesterone alone to support the luteal phase. In conclusion, the optimal stimulation protocol appears to be exogenous gonadotropin stimulation alone, without PS, and progesterone-only luteal phase support in CHH patients.

Impact of pre-treatment in GnRH-antagonist cycles triggered with GnRH agonist on reproductive outcomes.

OBJECTIVE: Pre-treatment (PT) therapies in IVF are known to be used as pre-stimulation modality to improve cycle outcomes. This study aims to assess whether PT in GnRH antagonist cycles triggered with GnRH-agonist impact oocyte maturation response. METHODS: Data were retrospectively collected for patients who underwent GnRH antagonist cycle with agonist triggering with and without PT. The patients were allocated to groups according to their PT status. The primary outcome evaluated was suboptimal maturation response. Suboptimal maturation to trigger was defined as no oocyte upon retrieval when adequate response was expected. RESULTS: The study population included 196 patients who underwent GnRH antagonist cycle with agonist triggering. The study group included 69 patients who received PT. The control group included 127 patients with no PT. In univariate analysis, the PT group significantly displayed suboptimal response compared to the controls (p = 0.008). All the patients in the study group with suboptimal response (with or without hCG re-triggering) were treated with GnRH-agonist as PT. Basal and pre-trigger LH values were significantly lower in the study group compared to controls (p < 0.001). Multivariate regression analysis revealed that PT with GnRH agonist was a significant predictor for suboptimal response. CONCLUSIONS: Pre-treatment, and particularly the use of GnRH-agonist as PT in antagonist cycles triggered with agonist, increases the risk of suboptimal response to GnRH-agonist trigger. This might be explained by prolonged pituitary suppression, which lasts beyond the PT cessation.

Pituitary Suppression with Gonadotropin-Releasing Hormone Agonist Prior to Artificial Endometrial Preparation in Frozen-Thawed Embryo Transfer Cycles: A Systematic Review and Meta-Analysis of Different Protocols and Infertile Populations.

This study investigates the effect of GnRHa pretreatment on pregnancy outcomes in artificial endometrial preparation for frozen-thawed embryo transfer (AC-FET) cycles. A systematic review of English language studies published before 1 September 2022, was conducted, excluding conference papers and preprints. Forty-one studies involving 43,021 participants were analyzed using meta-analysis, with a sensitivity analysis ensuring result robustness. The study found that GnRHa pretreatment generally improved the clinical pregnancy rate (CPR), implantation rate (IR), and live birth rate (LBR). However, discrepancies existed between randomized controlled trials (RCTs) and observational studies; RCTs showed no significant differences in outcomes for GnRHa-treated cycles. Depot GnRHa protocols outperformed daily regimens in LBR. Extended GnRHa pretreatment (two to five cycles) significantly improved CPR and IR compared to shorter treatment. Women with polycystic ovary syndrome (PCOS) saw substantial benefits from GnRHa pretreatment, including improved CPR and LBR and reduced miscarriage rates. In contrast, no significant benefits were observed in women with regular menstruation. More rigorous research is needed to solidify these findings.

Low Endogenous LH on the COS Initiation Day of a GnRH-Agonist Regimen Increases the Risk of Early Pregnancy Loss and Adverse ART Outcomes.

Objective: To assess the impact of serum luteinizing hormone (LH) levels on the day of initiation of controlled ovarian stimulation (COS) after pituitary suppression on early pregnancy loss and assisted reproductive technology (ART) outcomes. Design: Retrospective cohort study. Setting: University-affiliated hospital. Patients: A total of 9540 normogonadotrophic patients were treated with a GnRH agonist for in vitro fertilization (IVF). Based on the serum concentration of LH on the COS initiation day, patients were divided into low (<1 mIU/mL, n=2838), medium (1-1.49 mIU/mL, n=3357), or high (≥1.5 mIU/mL, n=3345) LH groups and received either fresh embryo transfer (ET) or frozen ET (women with high ovarian response, insufficient endometrial thickness, or requesting frozen ET). A total of 6279 cycles were fresh ET (1960, 2222, and 2097 in the low, medium, and high LH groups, respectively). Interventions: During IVF/ICSI, a GnRH agonist was used to suppress pituitary function in the midluteal phase or follicular phase, and then gonadotropin was used to induce COS. Main Outcome Measures: The early pregnancy loss rate (ePLR) and live-birth rate (LBR) for fresh ET, as well as the cumulative ePLR and LBR for the entire ovarian stimulation cycle, were compared. Results: In the fresh ET cycles, the high, medium and low LH groups had an ePLR of 8.6%, 11.9% and 12.5%, respectively, and LBR of 42.1%, 37.9% and 37.5%, respectively. There were no significant differences in terms of clinical pregnancy rate (CPR), late pregnancy loss rate (lPLR), and ectopic pregnancy rate (EPR) among the three LH groups. For the entire ovarian stimulation cycle, the high LH group had a greater number of retrieved oocytes compared with the low and medium LH groups. Among the groups of high, medium and low LH, the cumulative CPR were 72.8%, 69.8% and 68.8%, respectively, and the cumulative LBR were 63.4%, 60.4% and 58.5%, respectively. There were no significant differences in the cumulative ePLR, lPLR, or EPR. After multivariable logistic regression, compared with the high LH group, the adjusted odds ratio of early pregnancy loss in the low and medium LH group were 1.429 (1.065-1.919, P = 0.018) and 1.389 (1.041-1.853, P = 0.026). Conclusions: After pituitary suppression by a GnRH-agonist during IVF, a low LH level (<1.5 mIU/mL) on the COS initiation day was associated with adverse ART outcomes-including fewer oocytes, higher ePLR and lower LBR in fresh ET-and lower cumulative CPR and LBR in the entire ovarian-stimulation cycle. And LH on the COS initiation day was an independent factor affecting ePLR after multivariate regression.

Long-term pituitary downregulation before frozen embryo transfer improves clinical outcomes in women positive for serum autoantibodies.

OBJECTIVE: Autoantibodies are associated with worse outcomes in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), including increasing miscarriage rate, lowering pregnancy rate, and lowering delivery rate. However, little is known about improving IVF/ICSI outcomes for autoantibody-positive women, especially in frozen-thawed embryo transfer (FET) cycles. This study aimed to investigate whether pituitary suppression before FET improves the clinical pregnancy rate (CPR) and live birth rate (LBR) for IVF/ICSI women positive for serum autoantibodies. STUDY DESIGN: A total of 181 infertile women positive for serum autoantibodies were recruited, including 65 women receiving GnRHa and hormone replacement therapy protocols (G-HRT group) and 116 women using modified natural cycles (MNC)/mild stimulated cycles (MSC) as FET protocols (MNC/MSC group). The outcomes were compared between two groups, including CPR, implantation rate (IR), miscarriage rate (MR), ongoing pregnancy rate (OPR), LBR, and gestational age (GA). The primary outcome of the study was CPR. RESULTS: CPR, OPR, and LBR per embryo transferred in the G-HRT groups were significantly higher than those in the MNC/MSC group. No statistically significant differences were observed in the IR and MR. The CPR, IR, MR, OPR, and LBR was 72.23%, 64.00%, 12.77%, 63.07%, and 63.07% in the G-HRT group, respectively, while that was 56.90%, 53.07%, 10.60%, 50.00%, and 50.00% in the MNC/MSC group, respectively. After adjusting for partial potential confounding factors using multiple logistic regression, the type of endometrial preparation is the factor independently associated with enhanced CPR (OR = 0.48, 95%CI: 0.24-0.96, P = 0.039). CONCLUSIONS: The current study showed that prior long-term GnRHa suppression could benefit patients with high serum autoantibody levels during IVF/ICSI FET cycles.

Effect of GnRH analogues for pituitary suppression on oocyte morphology in repeated ovarian stimulation cycles.

OBJECTIVE: To compare the effect of pituitary suppression regimens on oocyte morphology in consecutive ICSI cycles of the same patients. METHODS: Data was obtained from 200 matched consecutive intracytoplasmic sperm injection (ICSI) cycles performed in 100 couples undergoing the first cycle with the GnRH agonist and the following cycle with the GnRH antagonist regimen, from January 2010 to August 2016, in a private university-affiliated IVF centre. The effects of the pituitary suppression type on oocyte morphology were assessed by multivariate General Linear Models. RESULTS: Mean interval between cycles was 185.32±192.85 days. Maternal age, body mass index, and total FSH dose administered were similar in both patients' cycles. Antagonist cycles presented lower incidence of dark cytoplasm (0.69±3.28% vs. 4.40±17.70%, p=0.047), Smooth endoplasmic reticulum (SER cluster (4.37±11.62% vs. 7.36±17.17%, p=0.046), and ZP defects (6.05±14.76% vs. 11.84±25.13%, p=0.049). Similar numbers of follicles retrieved oocytes, and mature oocytes were observed between the GnRH groups, as well as the fertilisation rate, number of obtained embryos, high-quality embryo rates, and the clinical outcomes. CONCLUSION: GnRH antagonist's inhibitory effect on the ovaries in consecutive ICSI cycles results in improved oocyte maturity and morphology, despite similar laboratory and clinical outcomes, compared to the GnRH agonist treatment.

Gonadotropin Releasing Hormone Agonists or Antagonists for Preimplantation Genetic Diagnosis (PGD)? A Prospective Randomised Trial.

BACKGROUND: The use of GnRH analogue medication is essential in reproductive medicine to avoid premature ovulation by pituitary suppression for the duration of ovarian stimulation by gonadotrophins. The type of pituitary suppression by either GnRH agonist analogues versus GnRH antagonist analogues may result in different embryological hence clinical results. Preimplantation genetic diagnosis is a subtype of IVF in which embryos are created for genetic diagnosis of hereditary disorders in order to avoid genetically affected children. Embryological quality hence ovarian stimulation in preimplantation genetic diagnosis is crucial as genetic selection will reduce the number of available embryos to a fraction of the total. OBJECTIVE: The aim of this study was to assess the efficiency of GnRH antagonist versus GnRH agonist treatment for pituitary suppression in ovarian stimulation for PGD, by proxy of number and quality of embryos at cleavage stage available for biopsy. METHOD: We conducted a prospective randomised controlled trial comparing pituitary suppression by GnRH antagonist versus GnRH agonist in ovarian stimulation for PGD. The primary outcome measure was the number of embryos of sufficient quality for biopsy at cleavage stage. Secondary outcome parameters were the number of blastocysts available of top quality, and clinical pregnancy rate. RESULTS: There was no difference in number of oocytes retrieved, embryos at cleavage stage available for biopsy or embryo quality. The clinical pregnancy rate was higher in the GnRH agonist group; however the sample size was insufficient to allow conclusions. CONCLUSION: The use of GnRH agonist versus antagonist treatment does not result in differences in a number of oocytes, embryos or embryo quality in ovarian stimulation for preimplantation genetic diagnosis.

Comparing stimulation requirements and final outcome between early follicular and mid luteal pituitary suppression in the long gonadotropin releasing hormone agonist protocol.

OBJECTIVE: To compare stimulation requirements and ICSI outcome when agonist treatment is started in the early follicular phase or in mid luteal phase of the cycle. METHODS: 181 infertile patients were randomly assigned to: group A (N=66) and group B (N=115). GnRH-a (Triptorelin) subcutaneous daily injections started on day 20-22 of the previous cycle till pituitary suppression is achieved where gonadotropins stimulation commenced. In group A, agonist treatment was started on the first or second days of the cycle, in group B it was started on day 20-22 of the cycle. The agonist treatment was continued till the day of (hCG) administration. RESULTS: The stimulation requirements were similar in the two groups. The days of t agonist treatment required to reach pituitary suppression were higher in group A: 12.5±6.4 than in group B, 11±4.5. Days of stimulation (10.4±1.7 and 10.3±1.6) and number of gonadotropin vials (40.1±8.7and 39.3±9.5) did not differ between both groups. The mean number of oocytes retrieved, mean number of embryos produced (11.7±7.4 and 13.3±9.3) (5.9±4.2and 6±5.2) were similar in both groups. The rates of fertilization and cleavage were similar in the two groups. Pregnancy rates were similar in both groups. The clinical pregnancy rates per cycle was 31.8% and 33%, while pregnancy rates per embryo transfer was 36.2 % and 36.5% in groups A and B respectively. CONCLUSION: Starting pituitary suppression with GnRH agonist in the early follicular phase or mid luteal phase were comparable regarding stimulation requirements and final outcomes.

Impact of pituitary suppression on antral follicle count and oocyte recovery after ovarian stimulation.

OBJECTIVE: To investigate the potential influence of short-term pituitary suppression on antral follicle count (AFC) and correlate the AFC with the number of oocytes retrieved after ovarian stimulation. DESIGN: Retrospective study. SETTING: University fertility center. PATIENT(S): A total of 1,479 infertile patients. INTERVENTION(S): Patients had baseline AFC, when they were not on any medications known to cause pituitary suppression, and follow-up AFC (suppressed AFC) while on E2, GnRH agonist (GnRH-a), oral contraceptive (OC) pills, or OC pills/GnRH-a in preparation for ovarian stimulation, performed within 6 months of initial baseline AFC. MAIN OUTCOME MEASURE(S): The AFC at baseline, AFC during pituitary suppression, and the number of oocytes retrieved. RESULT(S): Although there was an average unadjusted decline of 0.4, 0.9, 2.2, and 3.0 in AFC while patients were on E2, GnRH-a, OC pills, and OC pills/GnRH-a, respectively, this decline was driven by age, baseline AFC, and the hormones used. Although baseline and suppressed AFC were found to be good predictors of the number of oocytes retrieved after ovarian stimulation, statistically, suppressed AFC was found to be a marginally better predictor. CONCLUSION(S): Short-term pituitary suppression has a negative impact on AFC. This decline in AFC may influence the number of oocytes retrieved, suggesting the suppressive impact of exogenous hormones on the biological capacity of the ovary during stimulation.

Pituitary suppression before frozen embryo transfer is beneficial for patients suffering from idiopathic repeated implantation failure.

Long-term gonadotropin-releasing hormone agonist (GnRHa) administration before in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in infertile women with endometriosis or adenomyosis significantly enhanced the chances of pregnancy in both fresh and frozen embryo transfer cycles. We hypothesized that long-term GnRHa treatment might also be beneficial for the idiopathic repeated implantation failure (RIF) patients. In the 21 patients receiving GnRHa and hormone replacement therapy (G-HRT) protocols for frozen embryo transfer, their data were compared with those of the 56 of frozen/fresh cycles they had previously undergone (previous protocols). Comparison showed that the finial results were significantly better with G-HRT protocols than with their previous protocols, with pregnancy rate, clinical pregnancy rate, implantation rate and on-going pregnancy rate being 70%, 60%, 40% and 38% respectively with G-HRT protocols, against 17%, 11%, 6.3% and 5% with previous protocols. The results showed that hormonally controlled endometrial preparation with prior GnRHa suppression could be used for patients who had experienced repeated failures of IVF treatment despite having morphologically optimal embryos, and the treatment may help increase the receptivity of the endometrium in these patients.

Does lower dose of long-acting triptorelin maintain pituitary suppression and produce good live birth rate in long down-regulation protocol for in-vitro fertilization?

The effects of pituitary suppression with one-third depot of long-acting gonadotropin-releasing hormone (GnRH) agonist in GnRH agonist long protocol for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) were investigated. A retrospective cohort study was performed on 3186 cycles undergoing IVF/ICSI with GnRH agonist long protocol in a university-affiliated infertility center. The pituitary was suppressed with depot triptorelin of 1.25 mg or 1.875 mg. There was no significant difference in live birth rate between 1.25 mg triptorelin group and 1.875 mg triptorelin group (41.2% vs. 43.7%). The mean luteinizing hormone (LH) level on follicle-stimulating hormone (FSH) starting day was significantly higher in 1.25 mg triptorelin group. The mean LH level on the day of human chorionic gonadotrophin (hCG) administration was slightly but statistically higher in 1.25 mg triptorelin group. There was no significant difference in the total FSH dose between the two groups. The number of retrieved oocytes was slightly but statistically less in 1.25 mg triptorelin group than in 1.875 mg triptorelin group (12.90±5.82 vs. 13.52±6.97). There was no significant difference in clinical pregnancy rate between the two groups (50.5% vs. 54.5%). It was suggested that one-third depot triptorelin can achieve satisfactory pituitary suppression and produce good live birth rates in a long protocol for IVF/ICSI.

Anti-Mullerian as predictor of reproductive outcome in infertile women: follow up.

OBJECTIVE: The aim of the present study was to investigate and to compare the relations of anti-Mullerian with the prognostic parameters and the outcome of assisted reproductive treatment. METHODS: Prospective longitudinal study. A total of one hundred and twelve infertile women. Inclusion criteria: i) both ovaries present, ii) no current or past diseases affecting ovaries or gonadotropin or sex steroid secretion, clearance, or excretion, iii) no current hormone therapy, iv) adequate visualization of ovaries at transvaginal ultrasound scans, and v) total number of small antral follicles (3-12 mm in diameter) between 1 and 32 follicles. On cycle day 3, woman underwent blood sampling for serum FSH and AMH measurement and a transvaginal ovarian ultrasound scan for follicle measurement. Ongoing pregnancy was evaluated as biochemical pregnancy and observation of gestational sac(s). RESULTS: Mean age of 36.13 ± 4.65 years old, BMI 21.59 ± 2.78 kg/m2, and length of infertility of 2.88 ± 2.36 years. Their ovaries had an average of 13.74 ± 6.0 antral follicles and AMH was 2.49 ± 1.98 ng / mL. A significant relationship of AMH with age (r =-0.37 P <.01), with FSH (r =-0.22, P <.01), with AFC (r = 0.74, P <.00001), with smoking (P <.009), with SOP (P <.00001), with the total dose of the drug during stimulation ovarian (r =-0.36, P <.0004), with abortion (P <.05) and with the ongoing pregnancy (P <.05). CONCLUSION: AMH is a marker of quantitative and qualitative aspects of the ovarian reserve.