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Social elective egg freezing (EEF) is now widely used globally but in many countries is unaffordable to many women because of high costs and lacking insurance coverage. Efforts to reduce costs, therefore, are of importance. Surprisingly, a simple, well-defined and practical approach ensuring optimal outcomes for EEF has, however, so-far not been published. We, therefore, conducted a narrative review of the literature for relevant articles regarding the different steps of ovarian stimulation (OS) in the EEF process, in order to define such a standard protocol. This review revealed that in order to maximize oocyte yields with minimal number of OS cycles - while ensuring patient safety - a multiple-dose GnRH antagonist protocol with a daily gonadotropin dose of 300 IU appears best, unless patients demonstrate a polycystic ovarian phenotype, suggestive of likely high responses. The initial gonadotropin should be recFSH, while LH supplementation should be co-administered with the addition of GnRH antagonist. Final follicular maturation should be triggered by GnRH agonist trigger, with a dual trigger (1000-1500 IU hCG) considered for suboptimal responders to GnRH agonist trigger, optionally with Cabergoline to mitigate ovarian hyperstimulation syndrome (OHSS) in high responders., (© 2024. The Author(s).)

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: We aim to investigate the effect of extreme emotional and psychological trauma following Hamas terrorist attack on October 7th, 2023, on IVF cycle outcome., Patients and Methods: The study population consisted of all couples undergoing 2 consecutive IVF attempts with ovum pick-up in our institute, before and during the week of October 8th to 12th, 2023. Embryological/ laboratory variables of the IVF cycles were assessed and compared between the patients' IVF cycle before and those that underwent OPU during the spoken week., Results: Twenty-three couples were eligible for analysis. There were no differences between the cycles in the length of ovarian stimulation, total dose of gonadotropin used, and the peak estradiol and progesterone levels. Furthermore, while no differences were observed in the number of oocytes and mature oocytes retrieved or fertilization rate, the mean number of top-quality embryos per OPU (1.1 ± 1.7 vs. 2.2 ± 2.9; p < 0.02) and ratio of top-quality embryos per number of fertilized oocytes (0.5 ± 0.3 vs. 0.7 ± 0.2; p < 0.01) were significantly lower during the spoken week. Semen total motile count was significantly reduced during the spoken week., Conclusions: In the present study, we are witness to the effect of acute emotional and psychological trauma on IVF outcome, as reflected by its detrimental effect on sperm and embryo quality., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ovarian stimulation (OS) is one of the key factors in the success of in vitro fertilization-embryo transfer (IVF-ET), by enabling the recruitment of numerous healthy fertilizable oocytes and, thereby, multiple embryos. The Stop GnRH-agonist/GnRH-antagonist (GnRH-ag/GnRH-ant), which offers all the advantages of using long suppressive GnRH-ag, with GnRH-ant, is in my opinion a valuable addition to the armamentarium of OS protocols. It allows cycle programming, better follicular synchronization and offers successful outcome in a variety of challenging cases such as poor responders, Poseidon group 4 poor prognosis patients, those with elevated peak progesterone (P) serum levels, poor embryo quality or repeated IVF failures., (© 2023. The Author(s).)

Pretreatment medications/manipulations are offered to patients with poor ovarian response, aiming to prevent the occurrence of a spontaneous luteinizing hormone surge, increase the number of preantral and antral follicles, synchronize follicular development, and increase oocytes' yield and quality, with the consequent improvement in cycle outcome. Although early small human studies were encouraging, interpretation of the studies is compromised by variations in the type, dose, combination and duration of the pretreatment medications. Whether these measures would serve as valuable tools in the armamentarium for treating patients with poor ovarian response requires further, large prospective studies that should validate the specific mode/combination of pretreatment measures and identify, before initiating ovarian stimulation, the specific characteristics of women who might benefit from the specific regimen., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluates the effect of different modes of final follicular maturation triggering on the degree of apoptosis of granulosa cells (GCs) and the potential effect on progesterone secretion., Methods: Thirty patients undergoing controlled ovarian hyperstimulation for IVF who received hCG, GnRH agonist, or dual trigger for final follicular maturation were included in the study. Granulosa cells were obtained at the time of oocyte retrieval. The proportion of apoptotic cells was evaluated via TUNEL and immunohistochemistry., Results: The proportion of apoptotic cells was significantly higher in the GnRH agonist-alone group compared to hCG-alone and the dual trigger groups (13.5 ± 1.5% vs. 7.8% ± 1.8 vs. 10.1% ± 2, respectively, P < 0.01). Moreover, the expression of active-caspase-3 was also significantly increased in the GnRH agonist-alone group compared with the hCG-alone and the dual trigger groups (15.5% ± 2.9 vs. 8.4% ± 1.6 vs. 12.7% ± 2.6, respectively, P < 0.01). The progesterone levels measured in the granulosa-luteal cell culture medium after 24 h of incubation were similar between the three groups., Conclusions: The levels of apoptosis are increased after GnRH agonist/dual trigger. The increased apoptosis might be one of the culprit of the subsequent premature demise of the corpus luteum post GnRH agonist trigger., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Research Question: What is a suitable time interval between the last GnRH antagonist exposure and GnRH agonist (GnRHa) triggering for final follicular maturation?, Design: A retrospective cohort study including 413 patients undergoing GnRH antagonist cycles in which GnRHa trigger was used, either solely or as a dual trigger. The primary outcome measure was the follicle/mature oocyte ratio. Cycles were analysed according to the time interval between the last GnRH antagonist exposure and the GnRHa triggering: Group 1 included patients with a 12-14 h interval; Group 2: 7-10 h interval; Group 3: 5-6 h interval and Group 4: 2-4 h interval. LH concentration was measured 11-13 h post-GnRHa injection., Results: Median LH value was 65 IU/l. There was a weak but significant correlation between basal LH and the LH surge (R 2  = 0.137, P < 0.001). Although square root LH values differed significantly between study groups (P < 0.001; higher in Groups 2 and 3), the follicle/mature oocyte ratio was not different across the four antagonist-agonist interval groups and no correlation was detected between the post-trigger LH concentration and the follicle/oocyte ratio (R 2  = 0.011). In a model integrating age, day 3 FSH concentration, maximal oestradiol and body mass index along with the study groups, none of these factors was significantly related to the follicle/mature oocyte outcome ratio. Insufficient surge (LH < 15 IU/l) occurred in 14 (3.4%) cases. Rates of insufficient LH surge did not differ significantly between the groups (2.4%, 3.2%, 3.4% and 7.1% in Groups 1 to 4, respectively; P = 0.5)., Conclusions: LH concentrations post-GnRHa trigger differ in regard to antagonist-agonist intervals, but the follicle/mature oocyte ratio achieved was not affected., (Copyright © 2021. Published by Elsevier Ltd.)

Introduction: Several studies suggest that luteinizing hormone (LH) could improve IVF outcome in women of advanced reproductive age by optimizing androgen production. In this review, we assessed the role of recombinant-human LH (r-hLH) and recombinant human follicle stimulating hormone (r-hFSH) co-treatment in ovarian stimulation for assisted reproductive technology in women of advanced reproductive age candidates for assisted reproduction., Material and Methods: Using a preregistered protocol we systematically searched Medline/PubMed, Scopus and the ISI Web of Science databases to identify randomized controlled trials in which r-hFSH monotherapy protocols were compared with r-hFSH/r-hLH co-treatment in women ≥35 years undergoing fresh IVF cycles. We calculated the pooled odds ratio (OR) for dichotomous data and the weight mean difference (WMD) for continuous data with an associated 95% confidence interval (CI). The meta-analyses were conducted using the random-effect model. P values < 0.05 were considered statistically significant. Subgroup analyses of all primary and secondary outcomes were performed only in women aged 35-40 years., Results: Twelve studies were identified. In women aged between 35 and 40 years, r-hFSH/r-hLH co-treatment was associated with higher clinical pregnancy rates (OR 1.45, CI 95% 1.05-2.00, I 2  = 0%, P = 0.03) and implantation rates (OR 1.49, CI 95% 1.10-2.01, I 2  = 13%, P = 0.01) versus r-hFSH monotherapy. Fewer oocytes were retrieved in r-hFSH/r-hLH-treated patients than in r-hFSH-treated patients both in women aged ≥35 years (WMD -0.82 CI 95% -1.40 to - 0.24, I 2  = 88%, P = 0.005) and in those aged between 35 and 40 years (WMD -1.03, CI - 1.89 to - 0.17, I 2  = 0%, P = 0.02). The number of metaphase II oocytes, miscarriage rates and live birth rates did not differ between the two groups of women overall or in subgroup analysis., Conclusion: Although more oocytes were retrieved in patients who underwent r-hFSH monotherapy, this meta-analysis suggests that r-hFSH/r-hLH co-treatment improves clinical pregnancy and implantation rates in women between 35 and 40 years of age undergoing ovarian stimulation for assisted reproduction technology. However, more RCTs using narrower age ranges in advanced age women are warranted to corroborate these findings.

Background: A Delphi consensus was conducted to evaluate global expert opinions on key aspects of assisted reproductive technology (ART) treatment., Methods: Ten experts plus the Scientific Coordinator discussed and amended statements plus supporting references proposed by the Scientific Coordinator. The statements were distributed via an online survey to 35 experts, who voted on their level of agreement or disagreement with each statement. Consensus was reached if the proportion of participants agreeing or disagreeing with a statement was >66%., Results: Eighteen statements were developed. All statements reached consensus and the most relevant are summarised here. (1) Follicular development and stimulation with gonadotropins (n = 9 statements): Recombinant human follicle stimulating hormone (r-hFSH) alone is sufficient for follicular development in normogonadotropic patients aged <35 years. Oocyte number and live birth rate are strongly correlated; there is a positive linear correlation with cumulative live birth rate. Different r-hFSH preparations have identical polypeptide chains but different glycosylation patterns, affecting the biospecific activity of r-hFSH. r-hFSH plus recombinant human LH (r-hFSH:r-hLH) demonstrates improved pregnancy rates and cost efficacy versus human menopausal gonadotropin (hMG) in patients with severe FSH and LH deficiency. (2) Pituitary suppression (n = 2 statements): Gonadotropin releasing hormone (GnRH) antagonists are associated with lower rates of any grade ovarian hyperstimulation syndrome (OHSS) and cycle cancellation versus GnRH agonists. (3) Final oocyte maturation triggering (n=4 statements): Human chorionic gonadotropin (hCG) represents the gold standard in fresh cycles. The efficacy of hCG triggering for frozen transfers in modified natural cycles is controversial compared with LH peak monitoring. Current evidence supports significantly higher pregnancy rates with hCG + GnRH agonist versus hCG alone, but further evidence is needed. GnRH agonist trigger, in GnRH antagonist protocol, is recommended for final oocyte maturation in women at risk of OHSS. (4) Luteal-phase support (n = 3 statements): Vaginal progesterone therapy represents the gold standard for luteal-phase support., Conclusions: This Delphi consensus provides a real-world clinical perspective on the specific approaches during the key steps of ART treatment from a diverse group of international experts. Additional guidance from clinicians on ART strategies could complement guidelines and policies, and may help to further improve treatment outcomes., Competing Interests: TD and SL are employees of Merck KGaA, Darmstadt, Germany. RO received speaker fees/honoraria from Ferring and Merck KGaA, Darmstadt, Germany. CV is supported by a NHMRC Early Career Fellowship (GNT1147154). He also has equity interests in Virtus Health and reports grants, personal fees and non-financial support from Merck KGaA, Darmstadt, Germany, personal fees and non-financial support from MSD, grants and non-financial support from Ferring, personal fees from Besins Healthcare, and grants and non-financial support from Abbott. HF received speaker fees/honoraria/grants from MSD, Ferring, Besin, Merck KGaA, Darmstadt, Germany, and Sun Pharma. RF received consulting fees and honoraria from Merck KGaA, Darmstadt, Germany. YK received speaker fees/honoraria/grants from MSD, Merck KGaA, Darmstadt, Germany, Besins Healthcare, Gedeon Richter, Abbott, Bayer, and Sun Pharma. MH declares receipt of research grants from Merck KGaA, Darmstadt, Germany, and lecture fees from Merck KGaA, Darmstadt, Germany and Ferring. MG received fees from Merck KGaA, Darmstadt, Germany, Ferring, Gedeon Richter, MSD, IBSA. SE declares receipt of unrestricted research grants from Merck KGaA, Darmstadt, Germany, and lecture fees from Merck KGaA, Darmstadt, Germany, Gedeon Richter and Medical Education Academy. SS was speaker at non-promotional educational symposia by Merck KGaA, Darmstadt, Germany and Ferring in the last 12 months. YL received speaker fees/grants from Merck KGaA, Darmstadt, Germany, MSD, and Bayer. CA received consulting fees and payment/honoraria from Merck KGaA, Darmstadt, Germany., (Copyright © 2021 Orvieto, Venetis, Fatemi, D’Hooghe, Fischer, Koloda, Horton, Grynberg, Longobardi, Esteves, Sunkara, Li and Alviggi.)

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.)

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.)

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.

Research Question: To study the association between follicle size and oocyte/embryo quality, as a function of different triggering modes for final follicular maturation., Study Design: Cohort study conducted in a single tertiary medical centre between July 2018 and May 2019. All women undergoing ovarian stimulation with triggering using human chorionic gonadotrophin (HCG), gonadotrophin-releasing hormone (GnRH) agonist or dual trigger (GnRHa + HCG) were included. Before ultrasound-guided follicular aspiration, follicles were measured and divided into three groups according to maximum dimensions: large ≥16 mm, medium 13-15 mm and small <13 mm. Microscopic examination of the follicular aspirates was performed by an embryologist. Each follicle aspirated was evaluated for oocyte maturation, oocyte fertilization and embryo quality., Results: A total of 640 follicles were measured, including 402 (62.8%) in the large, 148 (23.1%) in the medium and 90 (14.1%) in the small groups. Oocytes were obtained during aspiration from 76.3%, 70.3% and 55.6% of the large, medium and small follicle groups, respectively (P = 0.001). The mature oocyte (metaphase II) rate was significantly higher in the large (P = 0.001) and medium (P = 0.01) compared with the small follicle group. Nevertheless, no between-group differences were observed in fertilization or top quality embryo rates among mature oocytes regardless of the size of the follicle from which they originated. Triggering mode did not influence oocyte recovery rate in the different follicle size groups., Conclusion: A higher oocyte recovery rate was observed from follicles >13 mm, however, mature oocytes achieved similar fertilization and top quality embryo rates regardless of follicle size. Triggering mode did not influence oocyte recovery rate., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

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.)

Studies on the role of LH supplementation in patients undergoing assisted reproductive technique use different sources of LH bioactivity-containing preparations, daily doses and modes of administration. This review aims to critically present the available evidence comparing the effect of the two commercially available LH preparations (human menopausal gonadotrophin [HMG] and recombinant FSH + recombinant LH) with different sources of intrinsic LH bioactivity (HCG versus LH, respectively) on ovarian stimulation characteristics and IVF cycle outcomes. A literature review was conducted for all relevant articles reporting on IVF and intracytoplasmic sperm injection treatment outcome after ovarian stimulation using HMG or recombinant FSH plus recombinant LH. The available studies are mostly observational, using different daily doses and modes of administration. No statistically significant differences were observed in ovarian stimulation variables and clinical pregnancy and live birth rates when HMG was compared with recombinant FSH + recombinant LH. Moreover, combined analysis of all the available prospective and retrospective studies produced no firm conclusions in favour of either source of LH bioactivity. Further large randomized controlled studies are needed to investigate the effect of the LH source on IVF outcome and to identify patients who are most likely to benefit from the addition of LH bioactivity supplementation., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

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.

Objective: To evaluate the influence of seasonal variation on in vitro fertilization (IVF) outcome in a large cohort population., Methods & Materials: A total of 5,765 IVF cycles conducted in Sheba medical center between 2013 and 2016 were retrospectively analyzed. The treatment cycles included 4214 ovarian stimulation and ovum pick up (OPU) cycles of which 3020 resulted in fresh embryo transfer and 1551 vitrified- warmed cycles of which1400 resulted in warmed embryo transfer. Cycles were assigned to seasons according to the date of OPU for fresh embryo transfer cycles or according to the date of embryo warming for vitrified warmed embryo transfer cycles., Results: There were no statistically significant differences between the calendar months or seasons concerning the number of oocytes retrieved or fertilization rate in the fresh cycles. Throughout the 4 years of the study, the monthly clinical pregnancy rate fluctuated between 18.2% and 27.9% per fresh embryo transfer (mean 23.3%) and between 17.7% and 29.4% per vitrified warmed embryo transfer (mean 23%). These fluctuations did not follow any specific seasonal pattern., Conclusions: Our study did not demonstrate any significant influence of the calendar months or seasons on the clinical pregnancy rates of fresh or vitrified warmed embryo transfers. It might be speculated that the complete pharmaceutical control of the ovarian and endometrial function, as well as the homogeneous treatments, procedures and laboratory equipment used during the study period have lowered the influence of seasonal effect on IVF treatment outcome., Competing Interests: The authors have declared no competing interests exists.

So-called mild controlled ovarian hyperstimulation (mCOH) has in recent years increased in popularity, claiming to be safer and more patient-friendly, while also improving in vitro fertilization (IVF) outcomes. We here challenge the International Society for Mild Approaches in Assisted Reproduction (ISMAAR) definition of mild stimulation, and especially address four fundamental issues, where our review found conventional COH (cCOH) advantageous over mCOH. They are: prevalence of severe ovarian hyperstimulation syndrome (OHSS), oocyte/embryo quality, pregnancy/live birth rates, and cost. We conclude that an objective review of the literature does not support the routine utilization of mCOH in assisted reproduction.

Objective: To investigate the messenger RNA (mRNA) expression of reproduction-related genes in granulosa cells (GCs) of patients triggered with hCG compared with patients triggered with GnRH agonist and hCG (double trigger) for final oocyte maturation., Design: Granulosa cells were obtained at the time of oocyte retrieval, and gene expression was analyzed using quantitative real-time polymerase chain reaction., Setting: Referral center., Patient(s): Fifteen women undergoing controlled ovarian hyperstimulation for IVF who received hCG for final follicular maturation and in a subsequent IVF cycle received double trigger., Intervention(s): Granulosa cells collection., Main Outcome Measure(s): The expression of genes related to ovarian hyperstimulation syndrome, gap junction, and epidermal-like growth factor in GCs., Result(s): The mRNA expressions of amphiregulin (2.1 vs. 1, arbitrary unit) and epiregulin (2.5 vs. 1, arbitrary unit) were significantly higher in the double trigger group compared with the hCG group. We found no difference in luteinizing hormone receptor and follicle stimulating hormone receptor mRNA expressions between the two groups. Moreover, although the mRNA expression of pigment epithelium-derived factor (1.5 vs. 1, arbitrary unit) was significantly higher in the double trigger group, no between-group differences were observed in the expression of vascular endothelial growth factor and GnRH receptor. The mRNA expression of conexin43 in cumulus cells (0.7 vs. 1, arbitrary unit) was significantly lower in the double trigger group compared with the hCG group., Conclusion(s): Our findings suggest that the decreased expression of conexin43 and the increased expression of epiregulin and amphiregulin in the GCs from patients receiving the double trigger may explain the suggested improved oocyte and embryo quality related to the double triggering group., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Recently, several new promising modifications have been introduced to clinical practice that may simplify and optimize IVF outcome. In the present opinion paper we present a simplified approach to controlled ovarian hyperstimulation protocol (COH), which combines the benefits of the ultrashort flare GnRH agonist/GnRH antagonist protocol and the personalized tailored mode and timing of ovulation triggering, aiming to improve IVF outcome while eliminating of severe OHSS.In patients at risk to develop severe ovarian hyperstimulation syndrome (OHSS), GnRH agonist (GnRHa) trigger if offered for final follicular maturation. While in those achieving ≥20 oocytes, the freeze all policy with the subsequent frozen-thawed embryo transfers (ET) is recommended, in those where less than 20 oocytes are retrieved, patients are re-evaluated 3 days after oocyte retrieval (day of ET) for signs of early moderate OHSS. If no early signs of OHSS developed, one embryo was transferred, and the patients are instructed to inject 1500 IU of HCG. In cases where signs of early moderate OHSS appear, the freeze all policy is recommended.In Patients not at risk to develop severe OHSS- three different modes of concomitant administration of both GnRHa and a standard bolus of hCG (5000-10,000 units) prior to oocyte retrieval were suggested. Standard hCG dose concomitant with GnRHa (dual trigger), 35-37 h before oocyte retrieval is offered to normal responders patients, resulting in improved oocyte/embryo quality and IVF outcome. GnRHa 40 h and standard hCG added 34 h prior to oocyte retrieval (double trigger), respectively are offered to patients demonstrating abnormal final follicular maturation despite normal response to COH. The double trigger results in significantly higher number of oocytes retrieved, higher proportions of the number of oocytes retrieved to the number of follicles >10 mm and >14 mm in diameter on day of hCG administration, higher number of MII oocytes and proportion of MII oocytes per number of oocytes retrieved, with the consequent significantly increased number of top-quality embryos, as compared to the hCG-only trigger cycles. Standard hCG dose concomitant with GnRHa (dual trigger), 34 h before oocyte retrieval should be offered to poor responders patients, aiming to overcome premature luteinization, while achieving high yield of mature oocytes.Further studies are required to support this new concept prior to its implementation as a universal COH protocol to IVF practice.

Objective: Human chorionic gonadotropin (hCG) is usually used at the end of controlled ovarian hyperstimulation (COH), as a surrogate LH surge, to induce final oocyte maturation and resumption of meiosis. Recently, the co-administration of GnRH agonist and hCG for final oocyte maturation - 40 and 34 h prior to OPU, respectively (double trigger) was suggested to improve IVF outcome in patient with genuine empty follicle syndrome. In the present study, we aim to evaluate whether the double trigger might improve the proportions of metaphase-II (MII) oocytes in patients with low proportion of mature oocytes (<66%) per number oocytes retrieved., Patients and Methods: We compared the stimulation characteristics of 12 IVF cycles, which include the cycle with the double trigger to the same patients' previous IVF attempt, triggered with hCG-only., Results: Patients who received the double trigger (study group) had a significantly higher number of mature oocytes - MII (6.5 versus 3.6 p < 0.008), number of embryos transferred (2.4 versus 1.1 p < 0.03), a significantly higher proportions of MII oocytes per number of oocytes retrieved (69.7% versus 47.1% p < 0.03) and a higher number of top quality embryos (3.1 versus 1 p < 0.02), as compared to their previous control cycles (hCG-only trigger). Six pregnancies were recorded in the study group and none in the control group., Conclusions: Co-administration of GnRH-agonist and hCG for final oocyte maturation, 40 and 34 h prior to OPU, respectively (double trigger) improves IVF outcome in patients with high proportion of immature oocytes.

Objective: We aim to evaluate the IVF-ET outcome in patients receiving a high daily dose (300 IU) of gonadotropins during controlled ovarian hyperstimulation (COH) for IVF and to assess the role of increasing the daily dose to 450 IU on improving outcome., Patients and Methods: All consecutive women admitted to our IVF unit during an 11 year period who underwent COH consisting of daily gonadotropin dose of 300 IU were included in the study. The ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and pregnancy rate were assessed. We also evaluated the subsequent cycle, using daily gonadotropin doses of 450 IU, among those patients who did not conceive using the 300 IU daily gonadotropin dose., Results: Nine hundred and forty-nine consecutive IVF cycles were evaluated. Patients who conceived using the daily gonadotropin dose of 300 IU (n = 133, 14% pregnancy rate) had significantly longer stimulation, yielded higher numbers of oocytes retrieved, fertilization rate and number of embryos transferred, compared to those who did not conceive. Moreover, while comparing IVF cycles using daily gonadotropin doses of 300 IU to 450 IU (n = 117), no in-between group differences were observed, except for significantly higher yields of oocytes retrieved. Moreover, cycles using daily gonadotropin doses of 450 IU resulted in a 7.7 live-birth rate., Conclusions: In poor responders undergoing COH with a daily gonadotropin dose of 300 IU, increasing the dose to 450 IU resulted in significantly higher oocyte yields and a reasonable live birth rate.

We aim to assess the in vitro fertilization-embryo transfer (IVF-ET) outcome in patients receiving an extremely high 450 daily dose (IU) of gonadotropins during controlled ovarian hyperstimulation (COH) for IVF. Moreover, in those who failed to conceive while using 450 daily dose (IU) of gonadotropins, we aim to evaluate whether increasing the daily dose gonadotropins to 600 IU will improve IVF outcome. All consecutive women, admitted to our IVF unit and underwent COH consisting of daily gonadotropin dose of 450 IU were included. Ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and pregnancy rate were assessed. Nine-hundred one consecutive IVF cycles were evaluated. While there was no between-group difference in the duration of COH, patients who conceived were significantly younger, yielded higher number of oocytes retrieved and embryos transferred and had significantly lower cancellations. In a sub-analysis, including only those patients who failed to conceive while using 450 daily dose (IU) of gonadotropins, and who underwent a subsequent IVF cycle attempt with the used of 600 IU daily dose of gonadotropins, no improvements in COH characteristics or cancellation rates were observed with increasing the daily gonadotropin dose to 600 IU. To conclude, in poor responders undergoing COH with an extremely high daily gonadotropin dose (450 IU), the most important factors that predict IVF success are female age and the number of oocytes retrieved. Moreover, patients who failed to conceive on a daily gonadotropin dose of 450 IU will not benefit from increasing the dose to 600 IU and should therefore consider the options of egg donation or adoption.

Background: Recently, the co-administration of GnRH agonist and hCG for final oocyte maturation- 40 and 34 hours prior to OPU, respectively (double trigger) was suggested as the treatment of genuine empty follicle syndrome. In the present study, we aim to evaluate whether the double trigger improves the number of oocytes retrieved in patients with low (<50%) number of oocytes retrieved per number of preovulatory follicles., Methods: In this proof of concept cohort historical study, we compared the stimulation characteristics of 8 IVF cycles, which include the double trigger to the patients' previous IVF attempt, triggered with hCG-only., Results: Patients who received the double trigger (study group) had a significantly higher number of oocytes retrieved, number of 2PN, number of embryos transferred and significantly higher proportions of the number of oocytes retrieved to the number of follicles >10 mm and >14 mm in diameter on day of hCG administration, with a tendency toward a higher number of TQE, as compared to their previous cycles (hCG-only trigger). Three ongoing clinical pregnancies were recorded in the study group and none in the hCG-only trigger group., Conclusions: Co-administration of GnRH-agonist and hCG for final oocyte maturation, 40 and 34 hours prior to OPU, respectively (double trigger), is suggested as a valuable new tool in the armamentarium for treating patients with low/poor oocytes yield despite an apparently normal follicular development and E2 levels and in the presence of optimal hCG levels on the day of OPU.

Objective: To evaluate the safety and efficacy of tamoxifen co-administration during conventional controlled ovarian hyperstimulation (COH) protocols for a fertility-preservation IVF cycle in breast cancer patients., Design: Two groups: retrospective descriptive cohort study and prospective study., Setting: Breast cancer oncology and fertility-preservation centers in a tertiary hospital., Patient(s): Two groups of breast cancer patients: premenopausal patients treated with adjuvant tamoxifen; and patients undergoing in vitro fertilization (IVF) for fertility preservation., Intervention(s): Fertility-preservation cycles, tamoxifen co-administration during conventional IVF., Main Outcome Measure(s): Endocrine records, and IVF results., Result(s): Estradiol (E2) levels were chronically high (mean 2663 pmol/L, maximum: 10,000 pmol/L) in 38 of 46 breast cancer patients treated with adjuvant tamoxifen. Co-administration of tamoxifen (48 cycles) during conventional IVF or without tamoxifen (26 cycles), using either the long gonadotropin-releasing hormone-agonist or-antagonist protocols, resulted, respectively, in a mean of 12.65 and 10.2 oocytes retrieved, and 8.5 and 6.4 embryos cryopreserved. Average peak E2 levels were 6,924 pmol/L and 5,093 pmol/L, respectively, but long-term recurrence risk (up to 10 years) was not increased., Conclusion(s): In breast cancer patients, co-administration of tamoxifen during conventional COH for fertility preservation does not interfere with IVF results. The high serum E2 levels during COH should be considered safe, as it simulates the high prevalence of persistently high serum E2 levels in premenopausal breast cancer patients safely treated with adjuvant tamoxifen., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To examine whether patients with poor ovarian response (POR) during conventional IVF/intracytoplasmic sperm injection (ICSI) treatment cycle may benefit from a modified natural cycle (MNC)-IVF., Design: Cohort historic study., Setting: Tertiary, university-affiliated medical center., Patient(s): One hundred eleven patients with POR, defined according to the Bologna criteria, who underwent a subsequent MNC-IVF within 3 months of the previous failed conventional IVF/ICSI cycle. The elimination of bias in this selection, for the purposes of this study, was achieved by including only a subgroup of "genuine" poor responder patients, those who yielded up to three oocytes after controlled ovarian hyperstimulation (COH) with a minimal gonadotropin daily dose of 300 IU., Intervention(s): Modified natural cycle IVF protocol with GnRH antagonist (GnRH-a) supplementation. Gonadotropin-releasing hormone antagonist treatment was started when a follicle of 13 mm was present. Two to three ampules of hMG were coadministered daily during the GnRH-a treatment., Main Outcome Measure(s): Live birth rate, pregnancy rate (PR), number of oocytes retrieved, and number of embryos transferred., Result(s): Live birth rate in "genuine" poor ovarian responders was <1%. Furthermore, in the subgroup of patients with POR who underwent a previous conventional IVF/ICSI cycle with a yield of only one oocyte, no pregnancies were achieved during the MNC-IVF cycle., Conclusion(s): Modified natural cycle-IVF is of no benefit for genuine poor ovarian responders and the option of egg donation should be seriously considered for this population., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Controlled ovarian hyperstimulation (COH) which combining GnRH antagonist co-treatment and GnRH agonist trigger with an additional 1500 IU hCG luteal rescue on day of oocytes retrieval, has become a common tool aiming to reduce severe ovarian hyperstimulation syndrome (OHSS). In the present, proof of concept study, we evaluate whether by deferring the hCG rescue bolus for 3 days, we are still able to rescue the luteal phase., Methods: Patients undergoing the GnRH-antagonist protocol, who were considered at high risk for developing severe OHSS and received GnRH-agonist for final oocyte maturation, were included. For luteal phase support, all patients received an "intense" luteal support. Those who had no signs of early moderate OHSS on day 3 after oocytes retrieval were instructed to inject 1500 IU of HCG bolus (hCG group). Ovarian stimulation characteristics and mid luteal progesterone levels were compared between those who received the HCG bolus and those who did not., Results: Eleven IVF cycles were evaluated, 5 in the hCG group and 6 in the intense luteal support only group. While no in-between group differences were observed in ovarian stimulation characteristics, significantly higher mid luteal progesterone levels (>127 nmol/L vs 42.1 ± 14.5 nmol/L, respectively) and a non-significant increase in pregnancy rate (40% vs 16.6%, respectively), were observed in those who receive the hCG bolus compared to those who did not., Conclusions: hCG luteal rescue should be offered 3 days after oocytes retrieval only to those patients with no signs of early moderate OHSS. Further studies are required to elucidate the appropriate regimen of luteal HCG administration in patients undergoing final follicular maturation with GnRH-agonist.

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.

The availability of gonadotrophin-releasing hormone (GnRH) antagonists for ovarian stimulation protocols has generated many meta-analyses comparing it to GnRH agonist long protocols. These meta-analyses have yielded conflicting results for pregnancy rate, with a tendency toward a better outcome for GnRH agonists. Recently, a Cochrane review seems to have settled the conflicts by demonstrating no evidence of statistically significant differences in the rates of live births or ongoing pregnancies when comparing GnRH agonist long protocols with GnRH antagonist protocols. This paper disputes the equivalence of these two protocols as discussed in the latest meta-analysis and argue that the GnRH agonist still has a demonstrable superiority over GnRH antagonist protocols. The availability of gonadotrophin-releasing hormone (GnRH) antagonist for ovarian stimulation protocols has generated many meta-analyses comparing it to GnRH agonist long protocols. These meta-analyses have yielded conflicting results for pregnancy rate, with a tendency towards a better outcome for GnRH agonists. Recently, a Cochrane review seems to have settled the conflicts by demonstrating no evidence of statistically significant differences in the rates of live births or ongoing pregnancies when comparing GnRH agonist long protocols with GnRH antagonist protocols. In this paper, we dispute the equivalence of these two protocols as discussed in the latest meta-analysis and argue that the GnRH agonist still has a demonstrable superiority over GnRH antagonist protocols., (Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

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.

In an attempt to evaluate the role of inositol supplementation in insulin-resistant patients with polycystic ovary syndrome (PCOS), undergoing gonadotropin ovulation induction using the low-dose step-down regimen, we conducted a prospective longitudinal study comparing the stimulation characteristics of 15 patients treated with inositol, to a cohort, matched by age and body mass index (BMI), without inositol. Inositol nutritional supplementation produced very good clinical results with a significant reduction in cancellation rate (0 vs. 40%) and the consequent improvement in clinical pregnancy rate (PR) (33.3% vs. 13.3%)., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

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.

To evaluate the influence of female age and cause of infertility on the outcome of controlled ovarian hyperstimulation (COH) and intrauterine insemination (IUI), we studied 2717 COH cycles in 1035 subfertile couples. The cumulative clinical pregnancy rates were 39% and 58% after three and six COH cycles, respectively. The cumulative pregnancy rate significantly decreased with maternal age and differed by cause of infertility. The cumulative pregnancy rate continued to increase with an increase in COH cycle number up to the third, or forth cycle, in patients with mechanical and combined infertility, respectively, and in up to the second cycle in patients aged 40 years or more. These findings provide treatment guidelines for clinicians in determining the likelihood of treatment success and the point at which to proceed to the next treatment strategy.

In an attempt to evaluate the effect of random timing of the start of clomiphene citrate (CC) treatment in anovulatory patients with polycystic ovary syndrome on treatment characteristics and outcome, with no regard to time of menstruation, we studied 291 women in their first CC treatment cycle. Duration of treatment was shorter by 2 days and number of leading follicles was higher when treatment was started late (7-29 days from starting a bleed, as compared with day 5), but no effect of starting day was observed on response rate to CC, maximal E(2) level, endometrial thickness, and pregnancy rate., (Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Aim: To evaluate the influence of smoking on the outcome of COH and IUI in subfertile couples., Patients and Methods: We reviewed the medical files of all consecutive women, age 14 mm in diameter, or E2 levels on the day of hCG administration., Conclusion: Smokers undergoing COH with IUI required a significantly higher gonadotropin dosage than nonsmokers in order to achieved a comparable pregnancy rate.

To examine whether and when conception may be achieved in multiple repeated in vitro fertilization cycles, we surveyed the outcome of 2760 consecutive cycles in our unit. The pregnancy rate statistically significantly decreased after the third cycle attempt, but no statistically significant decrease was observed between cycles 4 and 20; an acceptable clinical pregnancy rate/cycle of 15% was achieved between cycles 7 and 20.

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 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.

The failure of tests of ovarian reserve to predict clinical pregnancy in women 40 years old and older prompted this study of the predictive value of information obtained during the first cycle of in vitro fertilization (IVF). Stimulation characteristics during the first IVF cycle attempt were unhelpful in predicting the possibility of clinical pregnancy within the first three consecutive IVF cycles.