Dual trigger with gonadotropin-releasing hormone agonist and human chorionic gonadotropin significantly improves oocyte yield in normal responders on GnRH-antagonist cycles.

OBJECTIVE: During in vitro fertilization (IVF) cycles, final oocyte maturation is usually triggered by human Chorionic Gonadotropin (hCG) for its known effect in mimicking Luteinizing Hormone (LH) surge; however, with the widespread use of the 'antagonist protocol', Gonadotropin Releasing Hormone agonist (GnRHa) is being more commonly employed as a trigger in order to minimize or eliminate the risk of ovarian hyper-stimulation syndrome (OHSS). Many studies proved its efficacy in inducing oocyte maturation and its safety in preventing OHSS in high-risk groups. Moreover, some studies showed that GnRHa trigger may improve oocyte yield. This study aimed to further explore any beneficial effect of adding GnRHa to hCG (dual trigger) on oocyte yield and fertilization rate in normal responder women. METHODS: We retrospectively reviewed and analyzed the data from 127 patients on antagonist protocol (67 dual trigger and 60 HCG trigger). RESULTS: The number of total oocytes, the number of MII oocytes and the number of fertilized oocytes were all significantly higher with the dual trigger protocol compared to hCG-only trigger. However, there is no significant difference in clinical pregnancy rate. CONCLUSIONS: Using the dual trigger improved the number and quality of oocytes, and the fertilization rate in normal responders.

The ratio of exogenous Luteinizing hormone to Follicle stimulating hormone administered for controlled ovarian stimulation is associated with oocytes' number and competence.

We performed a retrospective study aiming to study the relationship between the ratio of the exogenous luteinizing hormone to follicle stimulating hormone (LH/FSH) administrated for controlled ovarian stimulation (COS) and the number and competence of the oocytes retrieved for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Eight hundred sixty-eight consecutive infertile patients (mean age 34.54 ± 4.01 years, mean anti-Müllerian hormone (AMH) 2.94 ± 2.07 ng/ml) treated with long agonist protocol and a mixed gonadotropin protocol (human menopausal gonadotropin in association with recombinant FSH (recFSH)) who performed IVF/ICSI between January 2013 and February 2016, were included. Patients with severe male factor were excluded. LH/FSH was calculated based on total doses of the two gonadotropins. We found, after adjustment for confounders, a positive relationship between LH/FSH and the retrieved oocytes' (ß = 0.229, P<0.0001) and zygotes' number (ß = 0.144, P<0.0001) in the entire study group and in subgroups according to age (<35 and ≥35 years) and ovarian reserve (AMH < 1.1 and ≥ 1.1 ng/ml). The fertilization rate was positively associated with LH/FSH in patients with LH/FSH in the lowest three quartiles (below 0.77) (ß = 0.096, P=0.034). However, patients in the fourth quartile of LH/FSH had a lower fertilization rate as compared with patients in quartiles 1-3 which, after adjustment for covariates, was only marginally negatively related with LH/FSH (ß = -0.108, P=0.05). In conclusion, our results suggest that the adequate LH/FSH administrated during COS can improve the oocytes' and zygotes' number in IVF/ICSI cycles, but also the fertilization rate when a certain proportion of LH/FSH is not exceeded.

The number of oocytes associated with maximum cumulative live birth rates per aspiration depends on female age: a population study of 221 221 treatment cycles.

STUDY QUESTION: What is the number of oocytes where the maximum cumulative live birth rate per aspiration (CLBR) is observed during ART in women of different ages? SUMMARY ANSWER: The maximum CLBR was observed when around 25 oocytes were retrieved in women between 18-35 years of age, around 9 oocytes in women more than 45 years of age and continued to increase beyond 30 oocytes in women between 36-44 years of age. WHAT IS KNOWN ALREADY: The live birth rate per fresh or frozen/thaw embryo transfer (FET) procedure has traditionally been the main measure of ART success. However, with the introduction of highly efficient embryo cryopreservation methods, CLBR encompassing live delivery outcomes from the fresh and all subsequent FET following a single ovarian stimulation and oocyte collection is increasingly viewed as a more meaningful measure of treatment success. There is evidence suggesting that larger oocyte yields are associated with increased likelihood of cumulative live birth per aspiration. Whether this association is the same across female ages has not yet been properly investigated. STUDY DESIGN, SIZE, DURATION: This is a large retrospective population-based cohort study using data from the Australian and New Zealand Assisted Reproduction Database (ANZARD). ANZARD contains information from all ART treatment cycles carried out in all fertility centres in Australia and New Zealand. Overall, 221 221 autologous oocyte aspiration cycles carried out between January 2009 to December 2015 were included in the analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cumulative live birth per aspiration was defined as at least one liveborn baby at ≥20 weeks gestation resulting from an ART aspiration cycle, including all fresh and FET resulting from the associated ovarian stimulation, until one live birth occurred or all embryos were used. Cycles where no oocytes were retrieved were excluded from analysis as there is no possibility of live birth. Analyses of data were performed using generalized estimating equations to account for the clustered nature of data (multiple cycles undertaken by a woman). Univariate and multivariable regression analysis was performed to identify and adjust for factors known to independently affect cumulative live birth per aspiration. An interaction term between female age and the number of oocytes retrieved was included to assess whether the age of the women was associated with a different optimal number of oocytes to achieve at least one live birth from an aspiration cycle (i.e. the effect-modifying role of female age). The likelihood of cumulative live birth per aspiration was calculated as odds ratios (ORs) with 95% CI. MAIN RESULTS AND THE ROLE OF CHANCE: The median number of oocytes retrieved was 7 (interquartile range, 4-12) and median age of patients was 36 (interquartile range, 33-40). The overall CLBR was 32.2%. The results from the multivariable regression analysis showedthat the number of oocytes retrieved remained a significant predictor (P < 0.001) of cumulative live birth per aspiration after adjusting for female age, parity and cycle count. Compared to the reference group of 10-14 oocytes retrieved, the adjusted odds for cumulative live birth per aspiration increased with the number of oocytes retrieved: 1-3 oocytes, 0.21 (95% CI, 0.20-0.22); 4-9 oocytes, 0.56 (95% CI, 0.55-0.58); 15-19 oocytes, 1.38 (95% CI, 1.34-1.43); 20-24 oocytes, 1.75 (95% CI, 1.67-1.84); and 2.10 (95% CI, 1.96-2.25) with more than 25 oocytes. After stratifying by female age group, the rate of increase in CLBR per additional oocyte retrieved was lower in the older age groups, indicating that higher oocyte yields were more beneficial in younger women. CLBR of patients in the <30 years and 30-34 years age groups appeared to reach a plateau (with only minimal increase in CLBR per additional oocyte retrieved) after retrieval of 25 oocytes at 73% and 72%, respectively, while CLBR of patients in the 35-39 years and 40-44 years age groups continued to increase with higher oocyte yields, reaching 68% and 40%, respectively, when 30 or more oocytes were retrieved. CLBR of patients aged 45 years and above remained consistently below 5%. Findings suggest that the number of oocytes retrieved where CLBR appears to be maximized is around 25 in women between 18-35 years, more than 30 in women between 36-44 years and around 9 in women 45 years and older. However, results for women aged 45 years and older may not be as robust due to the relatively small sample size available in this age group. LIMITATIONS, REASONS FOR CAUTION: As with all large retrospective database studies, there are potential confounders that cannot be accounted for. Despite the current study being based on complete ascertainment of ART cycles across two countries, ovarian stimulation protocols, oocyte quality parameters and a number of important patient characteristics are not collected by ANZARD. Additionally, a small number of cycles were available for women over 45 years yielding more than 15 oocytes, making these estimates unreliable. WIDER IMPLICATIONS OF THE FINDINGS: The results from this study demonstrate that the number of oocytes retrieved where the maximum CLBR is observed during ART is dependent on female age. This provides information for clinicians and patients to understand the modifying effect of age on the number of oocytes retrieved and the likelihood of success with ART. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. The Fertility Society of Australia funds the National Perinatal Epidemiology and Statistics Unit to manage ANZARD and conduct national reporting of ART in Australia and New Zealand. Associate Professor Georgina Chambers (G.C.) is employed by the University of New South Wales (UNSW) and is director of the National Perinatal Epidemiology and Statistics Unit at UNSW. G.C. was also a paid member of the Australian governments Medicare Benefits Scheme taskforce on assisted reproductive technologies in 2017.

The optimum number of oocytes in IVF treatment: an analysis of 2455 cycles in China.

STUDY QUESTION: What is the association between the number of oocytes retrieved and the live birth rate (LBR) following first IVF treatment cycles in China? SUMMARY ANSWER: In first IVF treatment cycles, the LBR after fresh transfer was maximal in the groups with 6-10 or 11-15 oocytes and reduced in the groups with 0-5 or >15 oocytes. Despite this, the cumulative LBR after including frozen embryo transfer cycles increased with an ovarian response. WHAT IS KNOWN ALREADY: There is a strong association between oocyte number and IVF outcome; however, this is a comprehensive analysis conducted to investigate the relationship between oocyte number and fresh cycle as well as cumulative LBRs in first IVF treatment cycles. STUDY DESIGN, SIZE AND DURATION: This is a large retrospective cohort study (n = 2455); patients were categorized into four groups according to the number of oocytes retrieved (0-5, 6-10, 11-15 and >15 oocytes). The fresh embryo transfer LBR and cumulative LBR were evaluated by group. Univariate analysis was performed to identify factors that predict the chance of LBR. Multivariate logistic regression was used to assess the association between oocyte number and LBR after adjusting for confounding factors that were identified as significant in the univariate analysis. PARTICIPANTS/MATERIALS, SETTING AND METHODS: A total of 2455 women who were undergoing their first IVF treatment cycle at the Reproductive Medicine Center of Anhui Provincial Hospital, P.R. China from April 2007 to December 2011 were identified and reviewed. All patients had normal menstrual cycles and were stimulated with a long GnRH agonist protocol. Associations between oocyte number and LBR and miscarriage rate as well as the rate of moderate-severe ovarian hyperstimulation syndrome (OHSS) were analyzed. MAIN RESULTS AND ROLE OF CHANCE: The fresh embryo LBR per started cycle increased with the number of retrieved oocytes up to Groups 2 and 3 (6-10 and 11-15 oocytes) and then decreased, because of the high number of cycles with all embryos being cryopreserved, in order to avoid moderate-severe OHSS in group 4 (>15 oocytes). However, the cumulative LBR per started cycle continued to increase with oocyte number, as did the incidence of moderate-severe OHSS. There was no significant difference in the miscarriage rates among the patient groups. LIMITATIONS, REASONS FOR CAUTION: As a retrospective study, our analysis depends on previously recorded data; therefore, certain variables could not be collected. Our findings may be influenced by our young and thin patient population and the inability to control for certain markers of ovarian reserve such as historical maximum serum FSH, antral follicle count and serum anti-Mullerian hormone. WIDER IMPLICATIONS OF THE FINDINGS: Our data suggest that in IVF cycles stimulated with a long protocol, the optimal number of oocytes for achieving a live birth is somewhere between 6 and 15. The balance between maximum treatment success and minimum risk of complications, especially OHSS, should be further investigated. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Medical Scientific Research Plan Project of Anhui Provincial Department of Health (13ZC014) and the Natural Science Foundation of Anhui Higher Education Institutions (KJ2013Z132).