Luteinizing Hormone Supplementation Research Articles

Luteinizing hormone supplementation in controlled ovarian stimulation: the Iran Delphi consensus.

Numerous consensus documents worldwide address luteinizing hormone (LH) supplementation in controlled ovarian stimulation, yet to the best of our knowledge, only one consensus paper has been published in the Arab region. This study presents a Delphi consensus by seven Iranian infertility experts, offering real-world clinical perspectives. The aim was to develop evidence-based opinions on LH's role alongside FSH in various aspects of assisted reproductive technology (ART), including LH levels, monitoring, r-hLH use, and suggested activity. Employing the Delphi consensus approach, the Iran consensus unfolded in three steps. In Step 1, eight out of 10 statements gained approval, while two unclear statements were removed. In Step 2, the 20-member extended panel voted on the remaining eight statements. Only one (statement 3) lacked consensus (55% agreement), prompting a modification. The revised statement (noted as statement 3') obtained an 83% agreement. The clinical perspectives included in this consensus complement clinical guidelines and policies that help further improve treatment outcomes, especially for patients with FSH and LH deficiencies.

LH supplementation in IVF: human nature, politics, and elephants in the room.

Luteinizing hormone (LH) is present throughout the natural follicular phase. However, the debate is still not settled on whether LH is needed during ovarian stimulation in IVF. This commentary looks at the evolution of this debate, mentioning three elephants in the room that were ignored by the Pharma industry, professional organizations, and clinicians alike: 1. The different endocrinology between the long agonist and the antagonist protocols. 2. The fixed dose of the two most widely commercially available antagonist preparations, namely cetrorelix and ganirelix. 3. The fact that most research in this area uses population-based criteria, ignoring endocrine parameters. Individual genetics of the LH receptor gene may also serve to individualize LH needs during stimulation; however, the jury is still out regarding this approach. CONCLUSIONS: Individual endocrine and genetics parameters may shed meaningful light on the question of LH supplemental during ovarian stimulation.

Luteinizing Hormone/Human Chorionic Gonadotropin Receptor N312S Single-Nucleotide Polymorphism and Its Impact on Clinical and Reproductive Outcomes in Assisted Reproductive Technology: A Prospective Cohort Study.

Objective The aim of this study was to determine the genotypic distribution of luteinizing hormone/human chorionic gonadotropin receptor (LHCGR) N312S single-nucleotide polymorphism (SNP) and to investigate its impact on clinical and reproductive outcomes in infertile Indian women undergoing assisted reproductive technology (ART). Study design and settings This was a prospective cohort study conducted at a tertiary care university hospital. Subjects and methods Infertile women aged between 21 and 40 years undergoing ART with an antagonist protocol were enrolled in this study. A 2-ml sample of peripheral venous blood was collected from each woman and genotyped for the LHCGR N312S SNP. Participants were divided into three groups based on their SNP: NN, NS, and SS. All subjects underwent controlled ovarian hyperstimulation (COH) through a gonadotropin-releasing hormone (GnRH) antagonist protocol and intracytoplasmic sperm injection (ICSI). Of the 140 women recruited based on selection criteria, 128 underwent embryo transfer. We compared the genotypic distribution of the LHCGR N312S SNP, baseline characteristics, clinical outcomes, and reproductive outcomes in ART among the three groups. Data were analyzed using IBM SPSS Statistics for Windows, Version 29 (Released 2022; IBM Corp., Armonk, New York, United States). The chi-square test and Fisher-Irwin test were employed to evaluate significant differences among the qualitative categorical variables. A p-value of less than 0.05 was considered statistically significant. Results Among the test subjects, 19.3% were homozygous for the LHCGR N312 SNP (NN group), 38.6% were heterozygous (NS group), and 42.1% were homozygous for the LHCGR S312 SNP (SS group). Baseline characteristics were similar among the three groups. In terms of ovarian reserve tests, significantly lower anti-Müllerian hormone (AMH) levels were observed in the SS group compared to the NS and NN groups (2.8 ± 2.1 vs. 3.2 ± 2.5 vs. 4.3 ± 3.3; p=0.03). No significant differences were observed in COH outcomes such as duration of stimulation, total gonadotropin requirement, oocyte yield, or the number of good-quality embryos among the three groups. The cumulative pregnancy rate (82.9% vs. 50.0% vs. 38.2%, p=0.0005), cumulative clinical pregnancy rate (78.8% vs. 44.7% vs. 34.5%, p = 0.0005), and cumulative live birth rate (50.0% vs. 20.2% vs. 20.0%, p=0.005) were significantly higher in the NN group than in the NS and SS groups. Conclusion The study's findings suggest that LHCGR N312 may help predict reproductive outcomes in ART, which may aid in providing better counseling to infertile couples. We need more studies on individualized/personalized COH using pharmacogenomics for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) supplementation based on combined FSH and LH receptor SNP and to assess their effects on ART outcomes.

P-639 Are our advanced maternal age population being affected by the shortage of HP-hMG?

Abstract Study question Could we stimulate patients of advanced maternal age in the face of a shortage of HP-hMG without impacting outcomes? Summary answer Given the current low availability of HP-hMG, it is safe to stimulate only with recombinant FSH in women of advanced maternal age without affecting results. What is known already . Studies on the role of luteinizing hormone (LH) supplementation in patients undergoing assisted reproductive treatments use different sources of LH bioactivity. It is well known that the addition of LH supplementation was associated with a tendency towards improved IVF outcome in specific profiles of patients undergoing Assisted Reproductive treatment. However, during the last quarter of 2022, we are facing a temporary fall in the global supply of HP-hMG, which has hCG-driven LH activity, and may impact ovarian stimulation outcomes in women of advanced maternal age undergoing a preimplantation genetic testing treatment (PGT). Study design, size, duration Retrospective and observational study during November-December 2022 in any of the 11 clinics belonging to the IVIRMA group in Spain. Study population included women ≥38 years undergoing PGT treatment who received monotherapy with recombinant FSH (n = 73), a combination of FSH + HMG containing an FSH: LH activity in a ratio 1:1 (n = 103), or a fertility drug with recombinant FSH + recombinant LH in a 2:1 ratio (n = 112). The study was approved by an IRB (2003-MAD-020-AR) Participants/materials, setting, methods All women underwent short GnRH antagonist protocol. Initial doses were adjusted based on weight and body mass index according to the clinician’s experience. Daily doses of 0.25 mg GnRH antagonist were started on day 6 of stimulation. Finally, a single dose of 0.2 mg GnRH agonist was administered to trigger final oocyte maturation. Embryo biopsy was performed on day 5 with a subsequent freeze-all. A frozen single embryo transfer was accomplished in a subsequent cycle. Main results and the role of chance Assuming the limitations of the study design, we observed significant differences in gonadotropin doses but not in retrieved oocytes, metaphase II oocytes or euploidy rate: the results were as follows for recombinant FSH, FHS + hMG and FSH + LH respectively: gonadotropin doses [2254 (692) vs. 2033 (680) vs. 2000 (660), p = 0.0035]; retrieved oocytes [10.1 (5.4) vs. 11.1 (8.0) vs. 9.2 (6.0), p = 0.131], metaphase II oocytes [8.7 (4.7) vs. 9.8 (7.1) vs. 8.3 (5.1), p = 0.147]; and euploidy rate (38.7% vs. 36.3% vs. 31.5%, p = 0.182). Moreover, recombinant FSH in monotherapy in this specific population could guarantee the efficiency of the cycle since there are no significant differences in the usable blastocyst rate. Finally, clinical results were analyzed in those cases in which a frozen single embryo had been performed in a subsequent artificial cycle, in which the effect of LH on the endometrium is obviated; once again, no significant differences were observed between the study groups neither for the implantation rate (50% vs. 56% vs. 45%, p = 0.780) or the clinical pregnancy rate (50% vs. 56% vs. 45%, p = 0.772). Limitations, reasons for caution This is a retrospective and observational study and thus possible confounders cannot be completely excluded. More data are needed to draw firm conclusions and it will be critical to increase the sample size to check if the results observed in this work remains in the general population. Wider implications of the findings In view of tailoring assisted reproductive protocols to meet patient needs and improve the likelihood of positive outcomes, these data suggest that it is optimal to perform an ovarian stimulation protocol only with recombinant FSH in a frozen embryo program in advanced maternal age context without clinical outcomes being affected. Trial registration number Not applicable

P-397 The effect of letrozole overlapped with gonadotropin on IVF outcomes in women with DOR or aged over 40 years old

Abstract Study question Evaluating the efficacy of modified letrozole protocol (mLP) for diminished ovarian reserve (DOR) or advanced age women. Summary answer The modified letrozole protocol provides another option for women with DOR or advanced age, especially those who experienced ovarian stimulation previously. What is known already For years, numerous methods have been conducted to obtain better outcomes in women with advanced age or DOR. Increasing doses of gonadotropin (Gn), exogenous luteinizing hormone (LH) or growth factor (GH) supplementation, and various kinds of controlled ovarian stimulation (COS) protocols were reported. However, there is still no consensus due to the contradictory reports of comparable reproductive outcomes. During ovarian stimulation, estrogen and androgen are important in the recruitment of primordial follicles and promotion of follicular growth at the preantral and antral stages across different species. Study design, size, duration This is a paired-match study including 243 women with DOR and 249 women aged over 40 years old who received in vitro fertilization (IVF) treatment. Participants/materials, setting, methods 123 women received stimulation with mLP. GnRH agonist (GnRH-a) long, GnRH antagonist (GnRH-anta), and mild stimulation protocol were used as controls with 123 women in each group. Clinical pregnancy rate (CPR) and cumulative clinical pregnancy rate (CCPR) were main outcomes. Main results and the role of chance CPR in the mLP group (38.46%) was significantly higher than mild stimulation (17.11%), but not significantly different from GnRH-a long (26.13%) and GnRH-anta (29.17%) group. CCPR showed an increasing trend in the mLP group (33.33%) although without significance when compared with controls. The CCRP of GnRH-a long, GnRH-anta, mild stimulation group were 21.68%, 29.03%, and 13.01%, respectively. In women with repeated cycles, mLP achieved higher available embryo rate and top-quality embryo rate. Further study showed positive correlation between testosterone and the number of oocytes retrieved in mLP group (r = 0.395, P< 0.01). Limitations, reasons for caution It is a retrospective study which resulted in minor bias among mLP and the other control protocols. Although we have already paired for age and AMH, the presence of biases cannot be totally excluded. Further prospective studies need to be done to validate the effect of mLP. Wider implications of the findings The modified letrozole protocol may be effective for women with DOR or advanced age, especially those who have experienced previous cycle failure. An increasing serum testosterone level may play a role and reflect follicular growth during ovarian stimulation. Trial registration number not applicable

The serum follicle stimulating hormone-to-luteinizing hormone ratios can predict assisted reproductive technology outcomes in women undergoing gonadotropin releasing hormone antagonist protocol.

The basal follicle stimulating hormone (FSH)/luteinizing hormone (LH) ratio is a useful predictor of ovarian response. In this study, we investigated whether the FSH/LH ratios during the entire controlled ovarian stimulation (COS) can be used as effective predictors of outcomes in women undergoing in vitro fertilization (IVF) treatment using the gonadotropin releasing hormone antagonist (GnRH-ant) protocol. A total of 1,681 women undergoing their first GnRH-ant protocol were enrolled in this retrospective cohort study. A Poisson regression model was used to analyze the association between the FSH/LH ratios during COS and embryological outcomes. Receiver operating characteristic analysis was performed to determine the optimal cutoff values for poor responders (≤ 5 oocytes) or poor reproductive potential (≤ 3 available embryos). A nomogram model was constructed to provide a tool for predicting the cycle outcomes of individual IVF treatments. The FSH/LH ratios (at the basal day, stimulation day 6 (SD6) and trigger day) were significantly correlated with the embryological outcomes. The basal FSH/LH ratio was the most reliable predictor of poor responders with a cutoff value of 1.875 (area under the curve (AUC) = 72.3%, P < 0.05), or of poor reproductive potential with a cutoff value of 2.515 (AUC = 66.3%, P < 0.05). The SD6 FSH/LH ratio predicted poor reproductive potential with a cutoff value of 4.14 (AUC = 63.8%, P < 0.05). The trigger day FSH/LH ratio predicted poor responders with a cutoff value of 9.665 (AUC = 63.1%, P < 0.05). The basal FSH/LH ratio, combined with the SD6 and trigger day FSH/LH ratios, slightly increased these AUC values and improved the prediction sensitivity. The nomogram provides a reliable model with which to assess the risk of poor response or poor reproductive potential directly based on the combined indicators. FSH/LH ratios are useful predictors of poor ovarian response or reproductive potential throughout the entire COS with the GnRH antagonist protocol. Our findings also provide insights into the potential for LH supplementation and regimen adjustment during COS to achieve improved outcomes.

Comparative Effects of Human Chorionic Gonadotropin and Recombinant Luteinizing Hormone Supplementation during the Late Follicular Phase

In selected patients, addition of LH activity can improve the outcome of ovarian stimulation. Two common LH activity supplementation strategies are recombinant human LH (rLH) and human chorionic gonadotropin (hCG). The respective effectiveness of hCG versus rLH using various daily dosages and modes of administration is still discussed. In this study, we compared the outcomes of hCG versus rLH supplementation among patients with slow response to recombinant follicle stimulating hormone (rFSH).

Effect of Exogenous Luteinizing Hormone (LH) Supplementation on Clinical Pregnancy of Patients Receiving Long-Acting Gonadotropin-Releasing Hormone Agonist (GnRHa) Cycles: A Retrospective Cohort Study.

Timely and moderate luteinizing hormone (LH) secretion plays critical roles in follicle development and maturation. However, the role of LH supplementation in in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) cycles remains unclear. Can LH supplementation improve the clinical outcomes of patients who receive long-acting gonadotropin-releasing hormone agonist (GnRHa) pituitary downregulation in IVF/ICSI-ET cycles? This is a retrospective cohort study of 2600 long-acting GnRHa down-regulated IVF/ICSI cycles from 2017 to 2020 in our reproductive medicine centre of Nanjing Drum Tower Hospital. Total cycles were divided into two groups according to LH supplementation or not. In addition, we conducted a secondary analysis that used propensity-score matching to reduce the effects of confounding. Exogenous LH addition was not significantly correlated with the clinical pregnancy rate (OR=0.910, 95% CI: 0.623-1.311, p=0.61) in logistic regression analysis. After propensity-score matching, we also found no significant association between LH supplementation and the clinical pregnancy rate (OR=0.792, 95% CI: 0.527-1.191, p=0.26). There is no obvious effect of exogenous LH supplementation on the clinical pregnancy rate in non-selective patients receiving long-acting GnRHa IVF/ICSI-ET cycles, which suggests that exogenous LH addition is not always needed, which can help us avoid drug overuse to a certain extent.

LUTEINIZING HORMONE SUPPLEMENTATION WITH HUMAN MENOPAUSAL GONADOTROPIN VERSUS LOW-DOSE HUMAN CHORIONIC GONADOTROPIN DURING STIMULATION DOES NOT AFFECT PREGNANCY OUTCOMES AFTER FRESH EMBRYO TRANSFER

To determine whether Luteinizing hormone (LH) supplementation with human Menopausal Gonadotropin (hMG) compared to low-dose human Chorionic Gonadotropin (LD-hCG) during controlled ovarian stimulation (COS) affects pregnancy outcomes after fresh embryo transfer (ET).

Luteinizing Hormone and Ovarian Stimulation for In-Vitro Fertilization: Do Science and Business Always Agree?

The current commentary paper follows the historical introduction of gonadotropins and gonadotropin releasing hormone (GnRH) analogues to the in-vitro fertilization (IVF) market. We maintain that business decisions significantly influenced research and development; however, pharma decisions did not always align with physiology and clinical interests. Specifically, the never-ending debate on the issue of luteinizing hormone (LH) supplementation during ovarian stimulation was repeatedly studied using population-based randomized controlled trials. However, LH activity supplementation is an endocrine issue and therefore, specific endocrine inclusion/exclusion criteria should be used when assessing the needs or not for LH in our “every-day” patients. We propose that the approach until now has defocused the research question and thus, also the debate and that there is a need to revisit physiology and clinical thinking if the LH supplementation issue is to be unravelled.

A retrospective, matched case-control study of recombinant LH versus hMG supplementation on FSH during controlled ovarian hyperstimulation in the GnRH-antagonist protocol.

BackgroundThe role of luteinizing hormone (LH) in controlled ovarian hyperstimulation (COH) requires more evidence for its efficacy. Several studies compared recombinant human LH (r-hLH) or human menopausal gonadotropin (hMG) in combination with recombinant human follicle-stimulating hormone (r-hFSH) but lack the results with GnRH-antagonist protocol and in Asians.MethodsThis is a retrospective, single-center study inspecting women receiving GnRH antagonist protocol and r-hFSH+hMG or r-hFSH+r-hLH regimen for over five days for COH in the in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle in Taiwan from 2013 to 2018. The outcomes of IVF/ICSI cycles were analyzed after propensity score matching between the two groups. A subgroup analysis was conducted in cycles in which women underwent their first embryo transfer (ET), including fresh ET and frozen ET (FET).ResultsWith a total of 503 cycles, the results revealed that the r-hFSH+r-hLH group performed better in terms of numbers of oocytes retrieved (r-hFSH+hMG vs. r-hFSH+r-hLH, 11.7 vs. 13.7, p=0.014), mature oocytes (8.7 vs. 10.9, p=0.001), and fertilized oocytes (8.3 vs. 9.8, p=0.022), while other outcomes were comparable. The analysis of first ET cycles also showed similar trends. Although the implantation rate (39% vs. 43%, p=0.37), pregnancy rate (52% vs. 53%, p=0.90), and live birth rate (39% vs. 45%, p=0.19) were not significantly different, the miscarriage rate was higher in the r-hFSH+hMG group than the r-hFSH+r-hLH group (26% vs. 15%, p<0.05) in first ET cycles. The cumulative pregnancy rate was significantly higher in the r-hFSH+r-hLH group (53% vs. 64%, p=0.02). No significant difference in rates of ovarian hyperstimulation syndrome (OHSS) was observed.ConclusionThe results support the hypothesis that the treatment of r-hLH+r-hFSH improves COH clinical outcomes in the IVF/ICSI cycle.

Effect of recombinant LH supplementation timing on clinical pregnancy outcome in long-acting GnRHa downregulated cycles

BackgroundTimely and moderate luteinizing hormone (LH) supplementation plays positive roles in in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) cycles with long-acting gonadotropin-releasing hormone agonist (GnRHa) pituitary downregulation. However, the appropriate timing of LH supplementation remains unclear.MethodsWe carried out a retrospective cohort study of 2226 cycles at our reproductive medicine centre from 2018 to 2020. We mainly conducted smooth curve fitting to analyse the relationship between the dominant follicle diameter when recombinant LH (rLH) was added and the clinical pregnancy outcomes (clinical pregnancy rate or early miscarriage rate). In addition, total cycles were divided into groups according to different LH levels after GnRHa and dominant follicle diameters for further analysis.ResultsSmooth curve fitting showed that with the increase in the dominant follicle diameter when rLH was added, the clinical pregnancy rate gradually increased, and the early miscarriage rate gradually decreased.ConclusionsIn long-acting GnRHa downregulated IVF/ICSI-ET cycles, the appropriate timing of rLH supplementation has a beneficial impact on the clinical pregnancy outcome. Delaying rLH addition is conducive to the clinical pregnancy rate and reduces the risk of early miscarriage.

Luteinizing hormone supplementation in women with hypogonadotropic hypogonadism seeking fertility care: Insights from a narrative review.

The management of infertile women affected by hypogonadotropic hypogonadism (HH) or conditions mimicking it is particularly challenging. In the present narrative review, we aimed to synthesize the available evidence on the benefit (if any) of exogenous luteinizing hormone (LH) supplementation in this group of patients. Available data support LH supplementation in women with organic or functional HH. On the contrary, the benefit of exogenous LH on reproductive outcomes both in advanced maternal age patients and in cases of depletion of FSH and LH levels induced by GnRH analogues has not been demonstrated. unfortunately, the inhomogeneous study populations as well as the methodological heterogeneity between studies focused on women affected by conditions mimicking HH do not allow reliable conclusions to be drawn.

Ovarian stimulation with luteinizing hormone supplementation: the impact of timing on ovarian response and ICSI outcomes.

To investigate whether the timing of rLH addition to rFSH during controlled ovarian stimulation (COS) impacts ovarian response and the outcomes of intracytoplasmic sperm injection (ICSI) cycles. Data of 1278 patients undergoing ICSI between 2015 and 2018, in a private university-affiliated IVF center were analyzed. Patients were divided into groups according to the timing of LH addition to the COS protocol: Group LH-start (n=323), in which LH was administered since day 1 of ovarian stimulation; and Group LH-mid (n=955), in which LH was administered concomitantly with gonadotropin releasing hormone (GnRH) antagonist. Data were also stratified according to female age and response to COS. The outcomes of COS and ICSI were compared between the groups. For the general group and in patients aged ≥ 35 years, higher blastocyst development rates were in Group LH-mid compared to Group LH-start. In patients with poor response to COS (POR), higher fertilization rate, blastocyst development rate and implantation rate were observed in Group LH-mid. rLH supplementation in POR patients may improve laboratorial and clinical outcomes when started in the mid-follicular phase, in GnRH antagonist ICSI cycles.

Improving Implantation Rate in 2nd ICSI Cycle through Ovarian Stimulation with FSH and LH in GNRH Antagonist Regimen.

To investigate whether patients with a previous recombinant follicle stimulating hormone (rFSH)-stimulated cycle would have improved outcomes with rFSH + recombinant luteinizing hormone (rLH) stimulation in the following cycle. For the present retrospective case-control study, 228 cycles performed in 114 patients undergoing intracytoplasmic sperm injection (ICSI) between 2015 and 2018 in an in vitro fertilization (IVF) center were evaluated. Controlled ovarian stimulation (COS) was achieved with rFSH (Gonal-f, Serono, Geneva, Switzerland) in the first ICSI cycle (rFSH group), and with rFSH and rLH (Pergoveris, Merck Serono S.p.A, Bari, Italy) in the second cycle (rFSH + rLH group). The ICSI outcomes were compared among the groups. Higher estradiol levels, oocyte yield, day-3 high-quality embryos rate and implantation rate, and a lower miscarriage rate were observed in the rFSH + rLH group compared with the rFSH group. In patients < 35 years old, the implantation rate was higher in the rFSH + rLH group compared with the rFSH group. In patients ≥ 35 years old, higher estradiol levels, oocyte yield, day-3 high-quality embryos rate, and implantation rate were observed in the rFSH + rLH group. In patients with ≤ 4 retrieved oocytes, oocyte yield, mature oocytes rate, normal cleavage speed, implantation rate, and miscarriage rate were improved in the rFSH + rLH group. In patients with ≥ 5 retrieved oocytes, higher estradiol levels, oocyte yield, and implantation rate were observed in the rFSH + rLH group. Ovarian stimulation with luteinizing hormone (LH) supplementation results in higher implantation rates, independent of maternal age and response to COS when compared with previous cycles stimulated with rFSH only. Improvements were also observed for ICSI outcomes and miscarriage after stratification by age and retrieved oocytes.

Protective Mechanism of Luteinizing Hormone and Follicle-Stimulating Hormone Against Nicotine-Induced Damage of Mouse Early Folliculogenesis.

Previous studies have shown that nicotine could impair the germ cell cyst breakdown and the primordial follicle assembly by autophagy. In this paper, we discovered that luteinizing hormone (LH) and follicle-stimulating hormone (FSH) could counteract the damage caused by nicotine of mouse germ cell cyst breakdown. The neonatal mice were separately intraperitoneally injected with nicotine, nicotine plus LH, nicotine plus FSH, and saline (control) for 4 days. Compared with the nicotine group, the quality of oocytes and the number of follicles were remarkably increased in the nicotine plus LH group or nicotine plus FSH group. LH and FSH could alleviate nicotine-induced oocyte autophagy by different pathways. LH reduced the nicotine-induced autophagy by restoring the phosphorylation level of adenosine 5′-monophosphate-activated protein kinase α-1, while FSH by downregulating the phosphorylation level of Forkhead box class O 1. In addition, in a subsequent study of 6-week mice in different treated groups, we found that LH and FSH supplementation significantly improved normal maturation rates, fertilization rates, and embryo’s developmental potential of oocytes in oocytes exposed to nicotine. Taken together, these results suggested that LH and FSH could counteract the damage caused by nicotine and finally ensure normal germ cell cyst breakdown and early embryo development.

P–594 Ovarian stimulation with luteinizing hormone supplementation: the impact of timing on ovarian response and ICSI outcomes

Abstract Study question Is there an impact of recombinant luteinizing-hormone (rLH) administration timing during controlled ovarian stimulation (COS) on ovarian response and intracytoplasmic sperm injection (ICSI) cycles outcomes? Summary answer rLH supplementation in patients with poor ovarian response (POR) improves laboratorial and clinical outcomes when started in the mid-follicular phase, in GnRH antagonist ICSI cycles. What is known already Meta-analyses demonstrated that the use of rLH combined with rFSH for COS may lead to more ongoing pregnancies than rFSH alone. However, there is limited evidence that the timing of rLH addition to rFSH may impact the ovarian response or the outcomes of ICSI, based on a limited casuistic, which demonstrated improved ovarian response, embryo quality and pregnancy rate with LH supplementation from GnRH antagonist administration day, in estimated POR patients. The objective of the present study was to further investigate this hypothesis in a larger population, and in subpopulations of patients stratified by age and response to COS. Study design, size, duration This historical cohort study included data obtained via chart review of 1278 ICSI cycles performed in 1278 patients between 2015 and 2018, in a private university-affiliated in vitro fertilization center. Post hoc power analysis was calculated, given α of 5%, sample size of 1278, and effect size for implantation rate. The achieved power was superior to 99%. Participants/materials, setting, methods Two groups were formed according to timing of LH administration: Group LH-start (n = 323), in which LH was started on day–1; and Group LH-mid (n = 955), in which LH was started with GnRH antagonist. Then, data were stratified according to female age (&amp;lt;35 years-old, n = 283, and ≥35 years-old, n = 995) and response to COS (poor response (POR): ≤4 retrieved oocytes, n = 423, and normal response: &amp;gt;5 retrieved oocytes, n = 855). Ovarian response and ICSI outcomes were compared among the groups. Main results and the role of chance In POR patients, significantly higher fertilization rate (68.3% ± 2.5 vs. 78.6% ± 3.7, p = 0.023), blastocyst development rate (22.5% ± 7.2 vs. 44.7% ± 6.2, p = 0.022) and implantation rate (17.6% ± 59.1 vs. 20.2% ± 43.2, p &amp;lt; 0.001) were observed in Group LH-mid, even though the amount of LH used in these patients was not significant different from that used in Group LH-mid from patients with normal response to COS (1062.35 IU ± 54.33 vs. 925.81 IU ± 414.41, p: 0.431, respectively). For the general group and in patients aged ≥ 35 years, higher blastocyst development rates were observed in Group LH-mid compared to Group LH-start (33.0% ± 31.9 vs. 40.8% ± 32.6, p = 0.012, and 28.8% ± 30.4 vs 38.5% ± 32.3, p = 0.006, respectively). In patients aged &amp;lt; 35 years and in those with normal response to COS, similar outcomes were obtained irrespective of timing of LH administration. Limitations, reasons for caution The limitations included the retrospective design and limited sample size in subpopulations. In addition, the reduced clinical outcomes related to POR patients may hamper the true estimation of the differences between the stimulation groups in terms of pregnancy and miscarriage rates. Wider implications of the findings: In POR patients, mid-follicular phase LH supplementation starting with 150 IU daily doses, may rescue the ongoing cycle by compensating an initial slow response, and balancing the deprivation of endogenous LH in GnRH antagonist cycles, with no need of expending more gonadotropin compared to patients with normal response to COS. Trial registration number Not applicable

The Importance of Mid-Follicular Phase Luteinizing Hormone Rise in GnRH Antagonist-Based Ovarian Stimulation for IVF

Introduction: Previous publications examined the endocrinology of follicular stimulation, focusing on luteinizing hormone (LH) levels changes. In selected, good prognosis IVF patients, a sharp drop in LH serum level was demonstrated between cycle days 2 and 6. Objective: The purpose of this study was to examine if this finding holds true for unselected patients. Methods: We retrospectively included 165 consecutive patients treated with a GnRH antagonist-based ovarian stimulation protocol during the year 2015. Results and Conclusions: In 33% of the patients an increase in LH, rather than the expected decrease, was demonstrated after 5 stimulation days. There was no difference in pregnancy outcome. Our results suggest that an increase in LH levels during ovarian stimulation occurs mainly in “high responders”, or “low responders”. LH rise in mid follicular phase may result in a sharp LH drop once a GnRH antagonist is given, and the possible need for LH supplementation.

Comparison of Highly Purified HMG versus Recombinant FSH with Antagonist Protocol in Poor Responder Patients

Background:Luteinizing hormone (LH) supplementation may have beneficial effect on the maturity and fertilizability of oocytes in poor ovarian reserve (POR) and may influence the progesterone level, thus increasing the pregnancy rate. However, previous studies on the effect of LH activity supplementation on poor responders have shown conflicting results. This study aimed to compare the clinical effectiveness of two different forms of gonadotropin (highly purified human menopausal gonadotropin (HP-HMG) vs. recombinant human follicle-stimulating hormone (r-hFSH)-only) in Indonesian population. Methods: Women diagnosed with poor ovarian response who received gonadotropin-releasing hormone (GnRH) antagonist protocol with either HP-HMG or r-hFSH-only were investigated. Women who underwent freeze all cycles, mini stimulation, and natural stimulation were excluded. Multiple logistic regression was performed to assess the effect of follicle-stimulating hormone (FSH) + human chorionic gonadotropin (HCG)-driven LH activity combination in HP-HMG to pregnancy event adjusting for progesterone level, demographic variables, and clinical characteristic variables. Results: A total of 101 subjects in the HP-HMG treatment group and 89 subjects in r-hFSH-only treatment group were involved in the study. There was no significant difference of clinical pregnancy rate between HP-HMG group and r-hFSH-only group (adjusted OR: 0.94, 95% CI: 0.39–2.25; p-value: 0.890). Conclusion: Compared to r-hFSH-only group, combination of FSH + HCG-driven LH activity in HP-HMG group had similar effectiveness in poor responders undergoing in vitro fertilization (IVF) using the antagonist protocol.

Use of luteinizing hormone supplementation for ovarian stimulation in IVF/ICSI cycles of women with good ovarian reserve

Use of luteinizing hormone supplementation for ovarian stimulation in IVF/ICSI cycles of women with good ovarian reserve