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Objective: Ovarian stimulation (OS) with high daily gonadotropin doses are commonly offered to patients attempting social/elective egg freezing. However, the optimal daily gonadotropin dose that would allow a higher oocyte yield in the successive IVF cycle attempt was not settled and should be determined., Patients and Methods: Data from all women admitted to our IVF unit for social/EEF, who underwent two consecutive IVF cycle attempts, with only those who used in the first attempt a starting daily gonadotropin dose of 300IU were analyzed. Patients characteristics and OS variables were used in an attempt to build a logistic model, helping in determining the daily gonadotropin dose that should be offered to patient during their second EEF attempt, aiming to further increase their oocyte yield., Results: Three hundred and thirteen consecutive women undergoing two successive IVF cycle attempts were evaluated. Using logistic regression model, two equations were developed using individual patient-level data that determine the daily gonadotropin dose needed aiming to increase the oocyte yield in the successive cycle. (a): X=-0.514 + 2.87*A1 + 1.733*A2-0.194* (E2/1000) and (b): P = EXP(X) / [1 + EXP(X)]., Conclusions: Using the aforementioned equations succeeded in determining the daily gonadotropin dose that might result in increasing oocyte yield, with an AUC of 0.85. Any additional oocyte retrieved to these EEF patients might get them closer to fulfil their desire to parenthood., (© 2024. The Author(s).)

Objective: Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) activate distinct intracellular signaling cascades. However, due to their similar structure and common receptor, they are used interchangeably during ovarian stimulation (OS). This study aims to assess if the source of LH used during OS affects IVF outcome., Patients and Methods: This was a cross sectional study of patients who underwent two consecutive IVF cycles, one included recombinant follicular stimulating hormone (FSH) plus recombinant LH [rFSH+rLH, (Pergoveris)] and the other included urinary hCG [highly purified hMG (HP-hMG), (Menopur)]. The OS protocol, except of the LH preparation, was identical in the two IVF cycles., Results: The rate of mature oocytes was not different between the treatment cycles (0.9 in the rFSH+rLH vs 0.8 in the HP-hMG, p = 0.07). Nonetheless, the mean number of mature oocytes retrieved in the rFSH+rLH treatment cycles was higher compared to the HP-hMG treatment cycles (10 ± 5.8 vs 8.3 ± 4.6, respectively, P = 0.01). Likewise, the mean number of fertilized oocytes was higher in the rFSH+rLH cycles compared with the HP-hMG cycles (8.5 ± 5.9 vs 6.4 ± 3.6, respectively, p = 0.05). There was no difference between the treatment cycles regarding the number of top-quality embryos, the ratio of top-quality embryos per number of oocytes retrieved or fertilized oocytes or the pregnancy rate., Conclusion: The differences in treatment outcome, derived by different LH preparations reflect the distinct physiological role of these molecules. Our findings may assist in tailoring a specific gonadotropin regimen when assembling an OS protocol., (© 2021. The Author(s).)

Objective: This study aimed to characterize those patients undergoing the stop gonadotropin-releasing hormone (GnRH)-agonist combined with multidose GnRH-antagonist protocol, with suboptimal response to GnRH-agonist trigger in in vitro fertilization (IVF) cycles., Design: This is a cohort study., Setting: The study was conducted in a university hospital., Patients: All consecutive women admitted to our IVF unit from February 2020 through November 2020 who reached the ovum pick-up stage were reviewed., Interventions: Triggering final oocyte maturation by GnRH-ag alone (GnRH-ag trigger group), or combined with hCG (dual trigger group), in patients undergoing the stop GnRH-agonist combined with multidose GnRH-antagonist protocol was performed., Main Outcome Measure: The main outcome measure was LH level 12 h after the trigger., Results: Five out of the 32 patients (15.6%) demonstrated suboptimal response as reflected by LH levels <15 IU/L 12 h after GnRH-agonist trigger. Moreover, while no differences were observed in oocyte recovery rate, maturity, or embryo quality between the different study groups (GnRH-ag trigger and dual trigger groups), those achieving a suboptimal response to the GnRH-agonist trigger (post-trigger LH <15 mIU/mL) demonstrated significantly higher number of follicles and peak estradiol levels at the day of trigger, compared to those with optimal response (post-trigger LH >15 mIU/mL)., Conclusions: The stop GnRH-agonist combined with GnRH-antagonist protocol enables the substitution of hCG with GnRH-ag for final oocyte maturation. However, caution should be taken in high responders, where the dual trigger with small doses of hCG (1,000-1,500 IU) should be considered, aiming to avoid suboptimal response (post-trigger LH levels <15 IU/L)., (© 2021 S. Karger AG, Basel.)

Objective: The objective of this study was to examine whether the combined Stop GnRH-agonist (GnRH-ag), letrozole priming, and multiple-dose GnRH-antagonist (GnRH-ant) protocol may improve in vitro fertilization/intracytoplasmic sperm injection cycle in poor ovarian responders (PORs)., Design: This was a historical cohort, proof of concept study under tertiary setting at University affiliated Medical Center., Patients: Five PORs fulfilling the POSEIDON Group 4 criteria were included., Main Outcome Measures: Number of oocytes retrieved, number of top-quality embryos (TQEs), and controlled ovarian hyperstimulation (COH) variables were the main outcome measures., Results: The combined Stop GnRH-ag, letrozole priming, and multiple-dose GnRH-ant COH protocol revealed significantly higher number of follicles >13 mm on the day of hCG administration and higher number of oocytes retrieved, with non-significantly more TQEs and a reasonable clinical pregnancy rate., Conclusions: The combined Stop GnRH-ag, letrozole priming, and multiple-dose GnRH-ant COH protocol is a valuable tool in the armamentarium for treating POSEIDON Group 4 patients. Further large prospective studies are needed to elucidate its role in POR and to identify the specific characteristics of women (before initiating ovarian stimulation) that will aid both fertility specialists' counseling and their patients in adjusting the appropriate COH protocol., (© 2021 S. Karger AG, Basel.)

Context: Gonadotropin-releasing hormone agonist (GnRH-a) serves as an alternative to human chorionic gonadotropin (hCG) to trigger final oocyte maturation, while it significantly reduces the risk of ovarian hyperstimulation syndrome (OHSS), probably by attenuating vascular/endothelial activation., Objectives: The objectives of this work are to compare the effect of different modes of final follicular maturation (hCG vs GnRH-a) following ovarian stimulation (OS) for in vitro fertilization (IVF) on endothelial function., Design and Setting: A prospective cohort study was conducted at a tertiary medical center., Participants: Patients age 37 years or younger, undergoing OS for IVF, were allocated into 2 groups according to the type of final follicle maturation: the hCG group (n = 7) or the GnRH-a group (n = 8)., Intervention: Endothelial function was assessed by measurement of the peripheral arterial tonometry in reaction to temporary ischemia at 3 study points: day 3 of menstrual cycle (day 0), day of hCG/GnRH-a administration (day trigger) and day of oocyte pick-up (day OPU). The ratio of arterial tonometry readings before and after ischemia is called the reactive hyperemia index (RHI). Decreased RHI (< 1.67) indicates endothelial dysfunction., Main Outcome Measures: The main outcomes measures of this study included endothelial function at 3 study points during OS with different modes of triggering final follicular maturation., Results: The mean RHI values at day 0 were within the normal range for all patients and comparable between both groups (hCG: 1.7 ± 0.3 vs GnRH-a: 1.79 ± 0.4, P = .6). All patients presented a decrease in RHI values on day trigger, which did not differ between the 2 groups (1.62 ± 0.3 vs 1.4 ± 0.2, respectively, P = .2). However, the hCG group demonstrated a further decrease in RHI on day OPU, whereas patients who received GnRH-a had restored normal endothelial function reflected by increased RHI values (1.4 ± 0.2 vs 1.75 ± 0.2, respectively, P = .03)., Conclusions: Triggering final follicular maturation with GnRH-a restored normal endothelial function, whereas hCG trigger resulted in a decrease in endothelial function., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Co-administration of letrozole during the first 5 days of ovarian stimulation was suggested to improve IVF outcomes in poor responders. We aimed to determine whether poor/sub-optimal responders might benefit from Letrozole co-treatment throughout the entire stimulation course., Methods: We retrospectively reviewed the medical files of women who demonstrated poor (oocyte yield ≤3) and sub-optimal (4 ≤ oocyte yield ≤9) ovarian response during conventional multiple-dose antagonist stimulation protocols and were co-treated in a subsequent cycle with 5 mg Letrozole from the first day of stimulation until trigger day. A self-paired comparison between gonadotropins-only and gonadotropins-letrozole cycles was performed., Results: Twenty-four patients were included. Mean patients' age was 39.83 ± 4.60 and mean day-3-FSH was 12.77 ± 4.49 IU/m. Duration of stimulation and total gonadotropins dose were comparable between the two cycle groups. Peak estradiol levels were significantly lower in gonadotropins-letrozole cycles (2786.74 ± 2118.53 vs 1200.13 ± 535.98, p < 0.05). Number of retrieved oocytes (3.29 ± 2.15 vs 6.46 ± 3.20, p < 0.05), MII-oocytes (2.47 ± 1.65 vs 5.59 ± 3.20, p < 0.05), 2PN-embryos (1.78 ± 1.50, 4.04 ± 2.74, p < 0.05) and top-quality embryos (0.91 ± 0.97 vs. 2.35 ± 1.66, p < 0.05) were significantly higher in the gonadotropins-letrozole cycles. Clinical pregnancy rate in gonadotropins-letrozole cycles was 31.5%., Conclusion: Letrozole co-treatment during the entire stimulation course improves ovarian response and IVF outcomes in poor/sub-optimal responders.

Objective: To examine whether the Stop GnRH-agonist combined with multiple-dose GnRH-antagonist protocol may improve conventional IVF/intracytoplasmic sperm injection (ICSI) cycle in poor ovarian response (POR) patients. Design: Cohort historical, proof of concept study. Setting: Tertiary, University affiliated Medical Center. Patient(s): Thirty POR patients, defined according to the Bologna criteria, who underwent a subsequent Stop GnRH-agonist combined with multiple-dose GnRH-antagonist controlled ovarian hyperstimulation (COH) protocol, within 3 months of the previous failed conventional IVF/ICSI cycle, were included. For the purposes of this study, we eliminated a bias in this selection by including only "genuine" poor responder patients, defined as those who yielded up to 3 oocytes following COH with a minimal gonadotropin daily dose of 300 IU. Main Outcome Measure(s): Number of oocytes retrieved, number of top-quality embryos, COH variables. Result(s): The Stop GnRH-agonist combined with multiple-dose GnRH-antagonist COH protocol revealed significantly higher numbers of follicles >13 mm on the day of hCG administration, higher numbers of oocytes retrieved, and top-quality embryos (TQE) with an acceptable clinical pregnancy rate (16.6%). Moreover, as expected, patients undergoing the Stop GnRH-agonist combined with multiple-dose GnRH-antagonist COH protocol required significantly higher doses and a longer duration of gonadotropins stimulation. Conclusion(s): The combined Stop GnRH-ag/GnRH-ant COH protocol is a valuable tool in the armamentarium for treating "genuine" poor ovarian responders. Further, large prospective studies are needed to elucidate its role in POR and to characterize the appropriate patients subgroup (before initiating ovarian stimulation) that may benefit from the combined Stop GnRH-ag/GnRH-ant COH protocol., (Copyright © 2020 Orvieto, Kirshenbaum, Galiano, Elkan-Miller, Zilberberg, Haas and Nahum.)

Aim: The aim of the study was to examine whether the Stop GnRH-agonist combined with multiple-dose GnRH-antagonist protocol may overcome progesterone elevation during the late follicular phase., Patients and Methods: A cohort historical, proof of concept study consisting of 11 patients with progesterone elevation (>3.1 nmol/L) during conventional IVF/intracytoplasmic sperm injection (ICSI), who underwent a subsequent Stop GnRH-agonist combined with multiple-dose GnRH-antagonist ovarian stimulation (OS) protocol, within 3 months of the previous failed conventional IVF/ICSI cycle., Results: The Stop GnRH-agonist combined with multiple-dose GnRH-antagonist COH protocol revealed significantly lower peak progesterone levels, with significantly higher numbers of follicles >13 mm in diameter on the day of hCG administration, oocytes retrieved, mature oocytes, and top-quality embryos, with an acceptable clinical pregnancy rate (18.2%)., Conclusions: The combined Stop GnRH-ag/GnRH-ant OS protocol is a valuable tool in the armamentarium for treating patients with progesterone elevation during the late follicular phase. Further large prospective studies are needed to validate our observation and to characterize the appropriate patients' subgroup, which might benefit from the combined Stop GnRH-ag/GnRH-ant COH protocol., (© 2020 S. Karger AG, Basel.)

We aim to retrospectively evaluate the role of increasing the gonadotropin daily dose from 450 IU/day to 300 IU twice a day on IVF-ET outcome in poor responder patients. All consecutive women admitted to our IVF unit and underwent COH consisting of daily gonadotropin dose of 450 IU, followed by an IVF cycle using 300 IU twice a day, were included. Ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and pregnancy rate was assessed. Twenty-three patients undergoing both cycles were evaluated. While there was no between-group difference in the duration of COH, number of 2PN embryos, fertilization rate and number of embryos transferred, patients receiving daily gonadotropin 300 IU twice a day achieved a significantly higher peak estradiol levels (3350.39 ± 2364.26 vs. 2223.74 ± 1299.91; p  < .03, respectively), and yielded significantly higher number of follicles >15 mm in diameter on day of hCG administration (3.2 ± 2.4 vs 1.8 ± 1; p  < .03, respectively) and higher number of oocytes retrieved (3.48 ± 2.54 vs 1.87 ± 1.1; p  < .02, respectively) with an acceptable live birth rate (5%). To conclude, in poor responders undergoing COH a daily gonadotropin dose of 450 IU, increasing the dose to 300 IU twice daily may result in higher oocyte yield, with the possible improvement in IVF outcome.

Many strategies are offered for the treatment of poor responders. However, no compelling advantage for one stimulation protocol over another has been hitherto established. In this study, we aimed to evaluate the role of different modes and timings of final follicular maturation trigger, on in vitro fertilization (IVF) cycle outcome of poor responder patients. In the present randomized controlled study, poor responder patients, according to the Bologna criteria, undergoing controlled ovarian hyperstimulation (COH) using the gonadotropin-releasing hormone (GnRH) antagonist protocol were randomly assigned to three different final follicular maturation trigger modes and timings: hCG 36 h before oocyte pick-up (OPU) (hCG trigger); GnRH agonist (GnRHag) 36 h before (OPU) and hCG on day of OPU (GnRHag trigger); and GnRHag and hCG, 40 and 34 h prior to OPU, respectively (double trigger). Pregnancy rate, number of oocytes, and top quality embryos (TQEs). Thirty-three poor responder patients were recruited and randomized to the different study groups. While there were no in-between groups' differences in patients' demographics and stimulation variables, patients in the double trigger group had a significantly higher number of TQE (1.1 ± 0.9 vs . 0.3 ± 0.8 and 0.5 + 0.7; p <.02) as compared to the hCG trigger and the GnRH-ag trigger groups, respectively, with an acceptable pregnancy rate. Double trigger offers an additional benefit to poor responder patients. Larger studies are required to support this new concept prior to its implementation to IVF practice.

Aim: We sought to evaluate the influence of subtle serum progesterone elevation on in vitro fertilization (IVF) cycle outcome and to assess the impact of the type of gonadotropin-releasing hormone (GnRH)-analogue used during controlled ovarian hyperstimulation (COH) on the probability of clinical pregnancy., Patients and Methods: We reviewed the files of all consecutive patients undergoing COH with either GnRH-agonist or antagonist in our IVF unit during a 10-year period and who had their peak serum progesterone levels determined on the day of human chorionic gonadotropin (hCG) administration., Results: Of the 2244 IVF cycles evaluated, 2103 had peak progesterone level of <1.5 ng/mL (normal-P group) and 141 of >1.5 ng/mL (high-P group) (6.28% of all the study population). Clinical pregnancy rate was significantly higher in the normal-P group (25.4% versus 16.6%; p < 0.006). Moreover, among the high-P group patients, the use of the long GnRH-agonist suppressive protocol (GnRH-ag) was more prevalent in patients who conceived as compared to those who did not (60.9% versus 39%, respectively; p < 0.05), with a tendency toward an increase pregnancy rate in those using GnRH-ag compared with GnRH-antagonist protocol (GnRH-antag; p < 0.059) COH protocols., Conclusion: While subtle progesterone elevation in patients undergoing COH using GnRH-antag COH protocols, should dictate embryo cryopreservation and cancelation of the fresh transfer, in those undergoing the GnRH-ag COH protocol, a fresh embryo transfer should be recommended.

Objective: To evaluate, whether Gonadotropin-releasing hormone-agonist (GnRH-agonist or GnRH-ag) trigger in patients undergoing the ultrashort GnRH-ag/GnRH-antagonist (GnRH-ant) protocol is as effective as in patients at high risk to develop severe ovarian hyperstimulation syndrome (OHSS), who undergo the multidose GnRH-ant protocol., Design: Cohort study., Setting: University hospital., Patients: All consecutive women aged ≤35 years admitted to our IVF unit from January 2011 to October 2011 who reached the ovum pick-up stage., Interventions: Triggering final oocytes maturation by GnRH-ag instead of hCG, in high-responder patients undergoing either the ultrashort GnRH-ag/GnRH-ant or the multidose GnRH-antagonist controlled ovarian hyperstimulation (COH) protocols., Main Outcome Measures: Ovarian stimulation characteristics, percentage of mature oocytes, fertilization and pregnancy rates., Results: No inbetween groups differences were observed in ovarian-stimulation related variable, percentage of mature oocytes, fertilization or pregnancy rates. No case of moderate-severe OHSS was reported in the study, or the control groups., Conclusions: Three consecutive doses of daily GnRH-ag administration at the beginning of ultrashort flare GnRH-ag/GnRH-ant COH protocol, did not interfere with the ability of the GnRH-ag to trigger final oocytes maturation at the end of the COH cycle.

In an attempt to evaluate whether high basal day-3 luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio affects IVF cycle outcome in polycystic ovary syndrome (PCOS) patients undergoing ovarian stimulation with either GnRH-agonist (n = 47) or antagonist (n = 104), we studied 151 IVF cycles: 119 in patients with basal LH/FSH <2 and 32 in patients with LH/FSH ≥ 2. The PCOS with high LH/FSH ratio achieved a non-significantly higher pregnancy rate using the GnRH-agonist (50% vs 17.9%, p = 0.2; respectively), as compared to the GnRH-antagonist protocols, probably due to the ability of the long GnRH-agonist protocol to induce a prolong and sustained reduction of the high basal LH milieu and avert its detrimental effect on oocyte quality and implantation potential.

Objectives: To examine and compare the effect of the two commercially available menotropins (highly purified-human menopausal gonadotropin (HP-hMG) and the traditional human menopausal gonadotropin (hMG)) on ovarian stimulation characteristics and in-vitro fertilisation (IVF) cycle outcome., Study Design: We studied 36 patients undergoing at least two controlled ovarian hyperstimulation cycles for IVF, with the same GnRH-analogue protocols, where one included HP-hMG and the other included hMG. Ovarian stimulation characteristics and outcome were compared between the two groups., Results: Patients in the HP-hMG group achieved significantly higher implantation (20.0% vs. 8.1%, p < 0.03; respectively) and pregnancy rates (47.2% vs. 19.4%, p < 0.009; respectively) compared to the hMG group. Although no in-between group difference was observed in the number of top-quality embryos per patient, the proportion of the total number of top-quality embryos per total number of generated embryos was significantly higher in the HP-hMG group (88/196 vs. 72/204, p < 0.049; respectively) as compared to the hMG group., Conclusions: Patients undergoing controlled ovarian hyperstimulation for IVF that includes HP-hMG preparations produce significantly higher implantation and pregnancy rates, as compared to the traditional hMG.

Aims: To determine serum retinol-binding rotein 4 (RBP-4) levels in polycystic ovary syndrome (PCOS) patients undergoing controlled ovarian hyperstimulation (COH) for an in vitro fertilization-embryo transfer (IVF-ET) cycle and the possible correlation to COH variables., Patients and Methods: 11 consecutive PCOS patients undergoing our routine IVF flexible multidose gonadotropin-releasing hormone (GnRH)-antagonist protocol. Blood was drawn three times during the COH cycle: (1) day 1 or 2 of menstruation, and prior to gonadotropin administration (Day-S) (Day-S); (2) day of or prior to human chorionic gonadotropin (hCG) administration (Day-hCG); and (3) day of ovum pick-up (Day-OPU). Levels of estradiol and serum RBP-4 were compared among the three time points. Serum RBP-4 was measured with a commercial immunoassay., Results: Results showed significantly lower levels of serum RBP-4 on Day-OPU and Day-hCG than on Day-S. Though significant correlations were observed between serum RBP-4 and body mass index, fasting glucose or glucose to insulin ratio, no correlations were found between serum RBP-4 and IVF treatment variables or pregnancy rate., Conclusion: While serum RBP-4 decreases during COH for IVF, there is apparently no correlation of serum RBP-4 levels with IVF treatment variables or outcome.

In an attempt to examine and compare the effect of the two commercially available recombinant FSH on ovarian stimulation characteristics and IVF cycle outcome, we studied 264 IVF cycles in patients with a favorable prognosis a priori, 198 in patients using follitropin-alpha, and 68 in patients using follitropin-beta. Although both groups achieved a comparable number of retrieved oocytes, the use of follitropin-beta was associated with a tendency toward a lower clinical pregnancy rate (PR), and with significantly higher E(2) levels despite the use of significantly lower total gonadotropin dose.

In an attempt to evaluate the influence of the GnRH analogue used during controlled ovarian hyperstimulation (COH) on the outcome of IVF cycles of polycystic ovary syndrome (PCOS) patients, we studied 152 IVF cycles. The PCOS patients undergoing COH using the GnRH agonist protocol (n = 50) showed a significantly higher pregnancy rate (36% vs. 19.6%, respectively), compared with the GnRH antagonist protocol (n = 102).

In an attempt to examine whether body mass index (BMI) may influence IVF outcome in polycystic ovary syndrome (PCOS) patients undergoing ovarian stimulation with either gonadotrophin-releasing hormone (GnRH)-agonist (agonist group) or antagonist (antagonist group), 100 IVF cycles were studied: 35 in the agonist and 65 in the antagonist groups. In both agonist and antagonist groups, patients with BMI < or = 25 kg/m(2) had a significantly higher fertilization rate compared with patients with BMI > 25 kg/m(2) (P < 0.02 and P < 0.01, respectively). Lean patients (BMI < or = 25) undergoing ovarian stimulation using the GnRH-agonist, demonstrated the highest pregnancy rate. In conclusion, in this series of PCOS patients undergoing IVFembryo transfer cycles, ovarian stimulation utilizing the midluteal long GnRH-agonist suppressive protocol yielded a higher pregnancy rate in lean patients, probably due to its ability to lower the high basal LH milieu and its detrimental effect on oocyte quality and implantation potential.

To examine whether day 3 LH level or FSH-LH ratio predict IVF outcome, we studied patients with a favorable prognosis a priori undergoing controlled ovarian hyperstimulation (COH) with GnRH agonist (agonist group; n = 131) or antagonist (antagonist group; n = 137). Although LH level could not predict IVF outcome, patients undergoing COH using the GnRH antagonist or agonist protocols with FSH-LH ratios >2 or >3, respectively, achieved significantly lower pregnancy rates (11.1% vs. 27.7% and 8.3% vs. 31.9%, respectively).

To examine whether the choice of the GnRH analogues used during controlled ovarian hyperstimulation (COH), may influence endometrial receptivity, we studied 712 IVF cycles, in patients undergoing COH with GnRH agonist or antagonist and with the transfer of at least one top-quality embryo. The GnRH agonist group showed significantly higher endometrial thickness and higher pregnancy rate, suggestive of a higher endometrial receptivity, compared with the GnRH antagonist group.