Outcomes of BRCA pre-implantation genetic testing according to the parental mutation origin: a cohort study.

BACKGROUND: The process of gamete formation and early embryonic development involves rapid DNA replication, chromosome segregation and cell division. These processes may be affected by mutations in the BRCA1/2 genes. The aim of this study was to evaluate BRCA mutation inheritance and its effect on early embryonic development according to the parental origin of the mutation. The study question was approached by analyzing in vitro fertilization cycles (IVF) that included pre-implantation testing (PGT-M) for a BRCA gene mutation. METHODS: This retrospective cohort study compared cycles of pre-implantation genetic testing for mutations (PGT-M) between male and female patients diagnosed with BRCA 1/2 mutations (cases), to a control group of two other mutations with dominant inheritance (myotonic dystrophy (MD) and polycystic kidney disease (PKD)). Results were compared according to mutation type and through a generalized linear model analysis. RESULTS: The cohort included 88 PGT-M cycles (47 BRCA and 41 non-BRCA) among 50 patients. Maternal and paternal ages at oocyte retrieval were comparable between groups. When tested per cycle, FSH dose, maximum estradiol level, oocytes retrieved, number of zygotes, and number of embryos available for biopsy and affected embryos, were not significantly different among mutation types. All together 444 embryos were biopsied: the rate of affected embryos was comparable between groups. Among BRCA patients, the proportion of affected embryos was similar between maternal and paternal mutation origin (p = 0.24). In a generalized linear model analysis, the relative oocyte yield in maternal BRCA patients was significantly lower (0.7, as related to the non BRCA group)(p < 0.001). Zygote formation and blastulation were not affected by the BRCA gene among paternal cases (P = 0.176 and P = 0.293 respectively), nor by paternal versus maternal BRCA carriage (P = 0.904 and P = 0.149, respectively). CONCLUSIONS: BRCA PGT-M cycles performed similarly compared to non-BRCA cycles. Inheritance rate and cycle parameters were not affected by the parental origin of the mutation.

Fertility preservation for women with ovarian endometriosis: results from a retrospective cohort study.

RESEARCH QUESTION: What is the outcome of fertility-preservation treatments in women with endometrioma, especially those with endometrioma larger than 4 cm? DESIGN: Retrospective cohort study. Women with definitive diagnosis of ovarian endometriosis (by histology or ultrasound), who underwent fertility-preservation treatment in two IVF units between 2016 and 2021, were included. As some women cryopreserved oocytes and other embryos, the primary outcome was the number of metaphase II (MII) oocytes retrieved. RESULTS: Seventy-one women with ovarian endometriosis (OMA) underwent 138 fertility-preservation cycles. The median age of patients was 31 years. Forty out of 71 (56%) women underwent at least one surgery for OMA before fertility-preservation treatment. Multivariate analysis of each patient's first cycle was used. Women who underwent OMA surgery before fertility-preservation treatment had a 51.7% reduction (95% CI 26.1 to 68.5, P = 0.001) in the number of MII oocytes compared with women with OMA who did not undergo surgery. Among a subgroup who did not undergo surgery, those with an endometrioma larger than 4 cm had similar anti-Müllerian hormone concentration (2.6 ng/ml versus 2.1 ng/ml), number of oocytes retrieved (9 versus 9) and number of MII oocytes (7.6 versus seven 7) compared with women with an endometrioma of 4 cm or less. CONCLUSIONS: Discussing fertility-preservation treatment options with patients with OMA is recommended, especially if surgery is planned.

Clinical pregnancy rates among anovulatory and oligoovulatory women after letrozole versus hormone replacement therapy in frozen-thawed embryo transfer cycles.

This cohort study investigated whether letrozole versus hormone replacement therapy (HRT) results in higher live birth rate among anovulatory and oligoovulatory women in frozen-thawed embryo transfer (FET) cycles. It was conducted from 1st February 2018 to 31st January 2019 and included 261 anovulatory and oligoovulatory women. Since letrozole has become an effective alternative to HRT cycles, 121 patients received letrozole in 121 cycles from 1st February 2018 to 31st January 2019 and were compared to 140 HRT FET cycles among 140 women from 1st February 2017 to 31st January 2018. The primary outcome was live birth rate. Secondary outcomes were clinical pregnancy, multiple pregnancy and miscarriage rates. Clinical pregnancy and live birth rates of transferred cleavage embryos were higher in the letrozole compared to the HRT group (36/65 (55.3%) vs. 20/110 (18.1%), p < 0.001) and (25/65 (38.4%) vs. 17/110 (15.4%), p < 0.001) respectively, whilst these rates were similar for transferred blastocyst embryos. Miscarriage and multiple pregnancy rates were similar between groups. The letrozole group was older than the HRT group (31.8 ± 5.1 vs. 29.9 ± 5.1 years, p = 0.002) and more smoked cigarettes (p = 0.035). Groups were similar regarding BMI, male versus non-male indication for fertility treatment, peak oestradiol levels, and numbers of oocytes retrieved, blastocysts, frozen and transferred embryos. Letrozole compared to HRT might improve live birth and clinical pregnancy rates among anovulatory and oligoovulatory women undergoing FET cycles.

Does fresh single embryo transfer outcome predict the result of a subsequent vitrified-warmed blastocyst of the same cohort?

Reflecting the current trends, the utilization of frozen-thawed transfer cycles has been steadily increasing worldwide; outcome predictors of these cycles are therefore a major research goal. Our aim was to investigate whether the outcome of a fresh single blastocyst transfer (SBT) can serve as a prognostic factor for the subsequent vitrified-warmed SBT originating from the same cohort. A retrospective cohort study was performed at a single unit. Non-donor fresh cycles were analyzed as predictors of the following vitrified-warmed cycle. Only SBTs were included. Cycles designated to a freeze-all policy and cycles involving pre-implantation genetic analysis were excluded. A total of 1127 vitrified-warmed single blastocyst cycles were included. The indications for artificial reproductive technologies were comparable across the study groups. Vitrified-warmed cycles following a live birth outcome in the fresh cycle were more likely to result in a clinical pregnancy than those following a fresh cycle, which failed to reach a live birth. The same trend was observed for live birth rate following vitrified-warmed transfer in the fresh cycle. After correcting for possible confounders, age and embryo quality were significantly correlated with the chance for a live birth, but the previous fresh cycle did not affect the results. We therefore conclude that after adjustment for age, embryo quality and number of previous oocyte retrieval cycles, the fresh cycle outcome was not a significant influential factor for the following vitrified-warmed cycle.

Gonadotropin releasing hormone agonist triggering for in vitro maturation cycles.

The objective was to evaluate the outcomes of in vitro maturation (IVM) cycles using gonadotropin releasing hormone agonist (GnRH-ag) triggering. A retrospective cohort of IVM cycles from January 2015 to December 2019 in a single university-affiliated centre was examined. Main outcome measures were: (i) IVM maturation rate; and (ii) IVM maturation result. Secondary outcome measures were: (i) metaphase II (MII) rate on the day of egg retrieval; (ii) final MII maturation rate; and (iii) pregnancy rates. A total of 98 IVM cycles were performed during the study period: 50 (51%) were triggered with GnRH-ag (17 received FSH priming and 33 did not) and 48 cycles (49%) were triggered by hCG (37 with FSH priming and 11 without). A significant (p = 0.01) difference was noticed in maturation rate on egg retrieval day, in favour of the GnRH-ag group, although not in the final maturation rate achieved. Pregnancy rates were comparable between treatment sub-groups. GnRH-ag triggering in IVM cycles is an optional triggering mode and can be considered an acceptable option, especially when fertility preservation is a concern. GnRH agonists resulted in higher maturation rate on day of oocyte retrieval, but no difference in the total maturation rate.

You are not in the army now! A field study on the impact of a Preparation for Civilian Life program on young soldiers.

Recent years have seen the implementation of educational programs aimed at developing future orientation and better employability skills, mostly for people new to or returning to the job market. In a field study, we investigated the impact of a 5-day program on reintegration to civilian life on young Israeli combat soldiers' time preferences, gratitude, patriotism, and perceptions of their combat experience. Questionnaires administered before and after the program revealed a positive effect on future orientation but a negative effect on gratitude and perceptions of the combat experience. Although the positive effect on future orientation is in line with the program design, the negative effects found should be taken into consideration when planning or improving similar educational programs.

The effects of the COVID-19 crisis on the subjective well-being of the Israeli population-monitored phase by phase.

The paper examined the effect of the pandemic outbreak of COVID-19 on the cognitive and affective components of subjective well-being (SWB) over time in Israel. Just before the first verified patient, we ran a survey of the general population that included questions concerning both components of SWB, self-rated health, income satisfaction, and other socio-demographic aspects. The same survey among different respondents from the same population during the lockdown period when no exit strategy had been conveyed, and for the third time when the exit strategy was publicized and began to be implemented. The findings show that the cognitive component of SWB, as measured by Cantril's Ladder, remained stable over the long term. The average respondent reported unchanged life evaluation even when the individual's negative feelings rose by 52%, and positive feelings fell by 16%. We show evidence for a structural change in the weighting of feelings and self-rated health in life satisfaction function.

Repeated GnRH agonist doses for luteal support: a proof of concept.

RESEARCH QUESTION: What are the safety and feasibility of repeated subcutaneous doses of gonadotrophin-releasing hormone (GnRH) agonist for luteal support in IVF cycles triggered by a GnRH agonist? DESIGN: In this prospective trial, patients exhibiting oestradiol concentrations of over 2500 pg/ml after use of a GnRH agonist for triggering ovulation were initially randomized to GnRH agonist luteal support (0.1 mg subcutaneously every other day, starting on day 3 after embryo transfer) or to a control group supported by 80 µg of recombinant human chorionic gonadotrophin (HCG) on day 3 after embryo transfer. All patients underwent a day 5 blastocyst transfer. Randomization to the HCG luteal support was stopped owing to two cases of ovarian hyperstimulation syndrome (OHSS) and the study was continued solely with GnRH agonist luteal support. RESULTS: The study included 39 women in the repeated GnRH agonist luteal support group and seven in the HCG micro dose group. There were no cases of OHSS among patients supported by a GnRH agonist, and no other adverse events were recorded. There were no cases of bleeding before the pregnancy test, and hence no cases of an insufficient luteal phase. A clinical pregnancy rate of 43.6% was achieved with GnRH agonist luteal support. Hormone dynamics during the stimulation cycle reflected rising LH and progesterone concentrations after the introduction of GnRH agonist support. CONCLUSIONS: Repeated doses of GnRH agonist every other day as a method of luteal support provided safe and effective luteal support for women who underwent GnRH agonist triggering in a GnRH antagonist IVF cycle.

Does stress affect IVF outcomes? A prospective study of physiological and psychological stress in women undergoing IVF.

RESEARCH QUESTION: What are the effects of physiological and psychological stress on fertility outcomes for women undergoing IVF? DESIGN: A prospective cohort study of 72 patients undergoing IVF in 2017 and 2018. Physiological stress was assessed by salivary cortisol measurements: (i) pretreatment, when the patient received the IVF protocol; (ii) before oocyte retrieval (follicular cortisol was also measured); and (iii) before embryo transfer. Emotional stress was evaluated at each assessment with the State-Trait Anxiety Inventory and a 1-10 Visual Analogue Scale (VAS, referred to as the 'Stress Scale'. Correlations between cortisol concentrations, psychological stress and IVF outcome were assessed. RESULTS: Salivary cortisol concentrations increased by 28% from pretreatment phase (0.46 ± 0.28 µg/dl) to maximum concentration on oocyte retrieval day (0.59 ± 0.29 µg/dl, P = 0.029) and then decreased by 29% on embryo transfer day (0.42 ± 0.23 µg/dl, P = 0.0162). On embryo transfer day, cortisol among women in their first cycle was higher than women who underwent more than one treatment (P = 0.024). Stress Scale score increased by 39% from pretreatment to a maximum score on oocyte retrieval day and then decreased by 12% on embryo transfer day. Salivary cortisol and Stress Scale were not related to subsequent embryo transfer, fertilization rate, embryo quality or clinical pregnancy rate. Follicular cortisol concentration was positively correlated with fertilization rate (r = 0.4, P = 0.004). CONCLUSION: It can be cautiously concluded that physiological and psychological stress do not negatively affect IVF outcomes. Moreover, high follicular cortisol concentrations might have positive effects on pregnancy rates.

Oocyte Donation From Donor Older Than 35 Years. Is It Worth Trying?

INTRODUCTION: Due to several reasons, in some countries commercial oocyte donation is not possible. Accordingly, patients should find their own donors who may be over 35 years. The aim of this study was to compare the results of oocyte donation from donors <35 years (young donors) and donors ≥35 years old (older donors). MATERIAL AND METHODS: A retrospective cohort study was conducted at a single academic reproductive center. We compared the results of oocyte donation from donors <35 years (345 cycles) and from donor ≥35 years old (83 cycles). We also performed subgroup analysis for single embryo transfer (SET) and fresh and frozen embryo transfers. RESULTS: Recipient demographic characteristics of the 2 groups were comparable. The age of the donors was 29.8 ± 3.9 years in the young donor group and 37.6 ± 2.1 years in the older donor group ( P < .0001). Pregnancy and implantation rates in the recipients from young donor group were statistically significantly higher than those from the older donor group (50.7% and 40.9% vs 38.3% and 23%; P = .04, P < .001). Cumulative pregnancy and live birth rates were significantly higher in the young donor group compared to the older donor group (86.1% vs 57.4% P < .0001 and 52.2% vs 33.3%, P = .02, respectively). Subgroup analysis showed comparable pregnancy and live birth rates for SET cycles (45.5% vs 40.4% and 25.0% vs 21.2%, respectively) and fresh cycles (54.7% vs 42.6% and 35.8% vs 29.6%, respectively). CONCLUSION: In nonanonymous oocyte donation programs, donation from older donors with good ovarian reserve is an acceptable approach when young donor is not available.

Fresh transfer of Day 5 slow-growing embryos versus deferred transfer of vitrified, fully expanded Day 6 blastocysts: which is the optimal approach?

STUDY QUESTION: In IVF cycles in which the entire embryo cohort is slow growing, is it optimal to perform fresh transfer in Day 5 or to extend the culture and transfer in subsequent vitrified-warmed cycles? SUMMARY ANSWER: The outcomes depend on the degree of embryo development on Day 5. WHAT IS KNOWN ALREADY: Slow-growing blastocysts have lower implantation potential when transferred in fresh cycles. It has been suggested that embryo-endometrial asynchrony could explain this finding. However, studies that compared Days 5 and 6 embryos in frozen embryo transfer (FET) cycles showed contradictory results. There is still a lack of evidence regarding the best approach, performing fresh transfer or deferring transfer and continuing culture until fully developed blastocysts are achieved, when the entire cohort of embryos is slow growing. STUDY DESIGN SIZE, DURATION: This was a retrospective study that included 477 women aged <40 years who underwent fresh Day 5 single embryo transfer of slow-growing embryos and subsequent FET cycles of fully expanded blastocysts (FEB) originating from the same IVF cycle between 2012 and 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included cycles in which the embryos either began blastulation by Day 5 of culture but did not reach the fully expanded stage (Gardner Stage III) or had delayed blastulation with only morula embryos present by Day 5 of culture. All of the subjects in the study underwent elective, single embryo transfer (slow or delayed blastocysts) on Day 5 and had at least one embryo that developed into a FEB on extended culture Day 6 that was suitable for vitrification. All subjects, regardless of the outcome of the fresh transfer, returned for at least one subsequent FET cycle of Day 6 embryos. MAIN RESULTS AND ROLE OF CHANCE: A total of 1070 embryo transfer cycles (fresh + FET) were included. Of them, 365 women had elective, fresh, single transfer of slow-growing blastocysts (Group I) and 112 had elective, fresh, single morula transfer (Group II). Groups I and II underwent a subsequent 457 and 136 FET cycles, respectively. The mean age of Group I was 33.8 ± 2.9 years, the proportion of Day 5 embryos that developed to FEB by Day 6 was 92%, and the number of blastocysts vitrified was 627 (average of 1.71 blastocysts per cycle). The outcomes of fresh and FET cycles were comparable regarding clinical pregnancy rate (CPR) (31.0 vs. 30.4%, P = 0.86) and live birth rate (LBR) (23.3 vs. 20.3%, P = 0.15). In Group II, the mean age was 35.8 ± 3.4 years and the proportion of morula embryos that developed to FEB by Day 6 was 72%. The number of blastocysts vitrified on Day 6 was 155 (1.38 per cycle). The transfer of fresh embryos in Group II resulted in significantly lower clinical pregnancy (5.3 vs. 30.1%, P < 0.001) and LBRs (1.8 vs. 20.5%, P < 0.001). The results did not change after controlling for possible confounding factors. LIMITATIONS AND REASONS FOR CAUTION: The retrospective design of the study is a major limitation. Although we compared the outcomes of embryos that originated from the same cohort, the FET cycles could have been overrepresented by older patients and those with poorer prognoses. Furthermore, the study included only cycles in which there were blastocysts available for cryopreservation on Day 6; therefore, the results were not be applicable for those who had mandatory Day 5 transfer with no embryos available for vitrification. WIDER IMPLICATIONS OF THE FINDINGS: Fresh transfer of embryos that begin blastulation on Day 5 results in similar outcomes to the transfer of FEB originating from the same cohort. However, in cases where only morula/compacting embryos are available by Day 5, extending culture until FEB are achieved and then performing subsequent FET will result in significantly higher LBRs. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Neutrophils to lymphocytes ratio and platelets to lymphocytes ratio in pregnancy: A population study.

BACKGROUND: Neutrophils to lymphocytes ratio (NLR) and platelets to lymphocytes ratio (PLR) are both inflammatory ratios that can be easily calculated from a simple blood count. They are frequently reported and tested as prognostic factors in several medical disciplines. Pregnancy involves special reference values for laboratory assays. OBJECTIVE: The aim of this study was to define pregnancy-related reference values for NLR and PLR according to trimester, background morbidity and according to the patient's age. STUDY DESIGN: A retrospective analysis of a large cohort undergoing community-based pregnancy surveillance between the years 2011-2016. Data were analyzed according to high-risk patient versus normal-risk patient. RESULTS: A total of 11,415 patients were included. Mean PLR and NLR values were 136.3±44.3, 2.6±1, respectively during the first trimester, 144.6±47.1, 4.0±1.4 respectively during the second trimester and 118.1±42.0, 3.5±1.2 respectively during the third trimester. No difference was detected between the high-risk and the normal population (P-values 0.3, 0.5 and 0.4 for PLR in each trimester respectively and 0.3, 0.4, 0.6 for NLR in each trimester, respectively). No differences were detected among parity categories. The correlation between patient's age and either PLR and NLR was a weak positive correlation (though statistically significant). Both PLR and NLR reached a maximum value during the second trimester. The differences between mean NLR and PLR between trimesters were significant (P <0.01 for all differences tested). PLR rises in the presence of anemia, reaching statistical significance (P-value for PLR in each trimester was <0.01). NLR showed an opposite trend (P-values for NLR were 0.4, 0.005 and 0.06 in each trimester, respectively). CONCLUSIONS: In our cohort, there were generally no differences between the high-risk and the normal population, excluding patients with a fibroid uterus or inflammatory bowel disease who presented a significantly elevated PLR through all trimesters. Both PLR and NLR reached a maximum value during the second trimester and were positively correlated with age. We anticipate that the population-based data will assist in providing accurate reference values for future research testing NLR and PLR measures during pregnancy.

Cumulative live birth rate following elective single blastocyst transfer compared with double blastocyst transfer in women aged 40 years and over.

This retrospective cohort study aimed to identify predictive factors for live birth following blastocyst transfer in women aged 40-43, and to compare the cumulative live birth rate (LBR) following elective single blastocyst (eSBT) and double blastocyst (DBT) transfer. The study included 411 women who had fresh blastocyst transfers on day 5. In stepwise logistic regression, independent predictive factors for live birth were: transferring fully expanded blastocysts (Gardner stage ≥3) (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.59-9.71) and transferring two blastocysts compared with a single blastocyst (OR 1.7, 95% CI 1.08-2.9). Maternal age was not found to be significant (OR 0.78, 95% CI 0.62-1.1). When comparing eSBT (n = 150) with DBT (n = 151), the DBT group achieved higher LBRs (26.5 versus 19.3%, P = 0.017) and higher multiple births (0 versus 17.5%, P = 0.02). However, the cumulative LBR was similar (28.0 versus 31.1%), with significantly lower multiple births in the eSBT group (0 versus 14.9%, P = 0.03). These results indicate that in women aged 40-43, when fully expanded blastocysts are achieved, maternal age is not a predictor for live birth, and eSBT can be performed without compromising cumulative LBRs.

Predictive value of serum HCG concentrations in pregnancies achieved after single fresh or vitrified-warmed blastocyst transfer.

Possible differences between serum HCG levels in pregnancies achieved after transfer of a single fresh or a vitrified-warmed blastocyst were evaluated. Out of 1130 single blastocyst transfers resulting in positive HCG results, 789 were single fresh blastocyst transfers and 341 single vitrified-warmed blastocyst transfers. The initial serum HCG levels of 869 clinical intrauterine pregnancies were evaluated, 638 after the transfer of a single fresh blastocysts and 231 after the transfer of a single vitrified-warmed blastocysts. The HCG levels from cycles resulting in a clinical intrauterine pregnancy were significantly higher after the transfer of a single vitrified-warmed blastocyst (383 ± 230 IU/l) versus a fresh transfer (334 ± 192 IU/l; P = 0.01). Threshold values for predicting a clinical pregnancy for a fresh blastocyst were 111 IU/l and for a vitrified-warmed blastocyst 137 IU/l. Our study shows that the overall beta-HCG levels are comparable after the transfer of a fresh or vitrified-warmed blastocyst, suggesting that vitrification most probably does not affect the ability of the embryos to produce beta-HCG. This study further shows that when clinicians counsel patients, they should take into account that higher HCG levels are needed after a vitrified-warmed blastocyst transfer to predict a clinical intrauterine pregnancy.

Obstetric and neonatal outcomes of pregnancies conceived after preimplantation genetic diagnosis: cohort study and meta-analysis.

Preimplantation genetic diagnosis (PGD) may pose risks to pregnancy outcome owing to the invasiveness of the biopsy procedure. This study compares outcome of singleton and twin clinical pregnancies conceived after fresh embryo transfers of PGD (n = 89) and matched intracytoplasmic sperm injection (ICSI) pregnancies (n = 166). The study was carried out in a single university affiliated centre. Because of the paucity of available data, a literature-based meta-analysis of studies comparing neonatal outcome of PGD and ICSI pregnancies was also conducted. In the retrospective cohort study, obstetric and neonatal outcome were available in 67 PGD and 118 ICSI pregnancies. Perinatal outcomes were comparable between PGD and ICSI pregnancies. Meta-analysis revealed similar outcomes, except for higher rate of low birth weight (<2500 g) neonates in ICSI twin pregnancies (RR 0.86, 95% CI 0.74 to 1.0). Mean birth weight, gestational age at birth, pre-term deliveries (<37 weeks) and malformations were all comparable. In this cohort study and subsequent meta-analysis, no association was found between PGD conceived pregnancies and risks of adverse neonatal or obstetrical outcomes compared with ICSI pregnancies. Hence, blastomere biopsy for PGD does not seem to increase the risk for adverse perinatal outcome compared with ICSI pregnancies.

What we learned from extended culture of 'rejected' day-3 cleavage stage embryos: a prospective cohort study.

BACKGROUND: To test whether poor quality day-3 embryos can undergo successful blastulation and implantation. METHODS: A prospective cohort study was conducted. Whether or not a good quality embryo was transferred on day-3, poor quality (rejected) embryos were further cultured and followed. The clinical outcome of each embryo was assessed. RESULTS: A total of 694 rejected embryos (from 205 patients) were included, with a blastulation rate of 21.2% (147 embryos) compared to 64.2% general blastulation rate reported by our laboratory (P < 0.01). In a multivariate logistic regression model, only their grade on day-3 significantly affected blastulation (P = 0.01). A total of 97 embryos attained eligibility for fresh transfer or cryopreservation, only 6 of which resulted from a day-3 embryo scored < 2. Of these, 52 were transferred, resulting in 21 pregnancies (16 clinical and 5 chemical). In summary, 694 cultured embryos yielded 16 clinical pregnancies; a 2.3% clinical pregnancy rate. CONCLUSIONS: Low score day-3 embryos can result in successful blastulation and clinical pregnancies. However, the normal blastulation rate is poor.

Reproductive outcomes after a single dose of gonadotropin-releasing hormone agonist compared with human chorionic gonadotropin for the induction of final oocyte maturation in hyper-responder women aged 35-40 years.

OBJECTIVE: To investigate the reproductive outcomes after the use of GnRH agonist (GnRHa) compared with hCG for the induction of final oocyte maturation in GnRH antagonist cycles performed in hyper-responder women aged 35-40 years. DESIGN: Retrospective study. SETTING: Academic fertility center. PATIENT(S): Two hundred seventy-two hyper-responder women aged 35-40 years who underwent controlled ovarian stimulation under GnRH antagonist suppression were included. Final oocyte maturation was performed with GnRHa (n = 168) or hCG (n = 104). Embryos were cryopreserved at the blastocyst stage and transferred in subsequent warming cycles (n = 542). Subjects were included in the analysis until live birth was achieved, after which they were excluded from further analysis. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Cumulative live birth rate. RESULT(S): Subjects in the GnRHa group achieved a higher number of oocytes (22 vs. 21) and a higher number of mature oocytes (16 vs. 14). The number of cryopreserved blastocysts (median of five blastocysts in both groups) was similar. Women in the hCG group needed a lower number of warming cycles to achieve live birth (1.32 vs. 2.12), had higher embryo implantation rates (48% vs. 39%), and the proportion of embryos transferred until live birth was lower (33% vs. 57%). The cumulative live birth rate was similar between the groups (48.15% vs. 48%). CONCLUSION(S): Although the cumulative live birth rate is similar, a single dose of GnRHa possibly results in suboptimal oocyte and embryo competence, as manifested by decreased embryo implantation rates and increased time needed to achieve live birth.

Vitrified-warmed single-embryo transfers may be associated with increased maternal complications compared with fresh single-embryo transfers.

Cryopreservation of embryos allows single-embryo transfer and storage of supernumerary embryos, maximizing cumulative pregnancy rates. The purpose of this retrospective cohort study was to compare pregnancy outcome in singletons born after fresh or vitrified-warmed single blastocyst transfer (SBT). Singleton live births resulting from SBT of fresh or vitrified-warmed embryos were compared. Primary outcomes were perinatal outcomes including small for gestational age (SGA), low birthweight, preterm deliveries (PTD), large for gestational age (LGA) and congenital malformations. Maternal complications included pre-eclampsia, placenta previa, placental abruption, gestational diabetes mellitus (GDM) and chorioamnionitis. Adjustment for confounding factors was performed. Of 1886 fresh SBTs and 1200 vitrified-warmed SBTs during the study period, vitrified-warmed SBTs compared with fresh SBTs resulted in significantly lower clinical pregnancy rate (P < 0.0001). Live birth and miscarriage rates calculated only for pregnancy with known outcome revealed lower live birth rates and higher miscarriage rates for the vitrified-warmed group. Perinatal complications were calculated for clinical pregnancies with known outcomes (12.9% catchment failure was excluded from analysis). The vitrified-warmed group showed a trend toward higher rates of pre-eclampsia, GDM, Caesarean delivery and LGA neonates. Rates of PTD and SGA were comparable. In conclusion, vitrified-warmed SBT might be associated with increased feto-maternal complications.

Can we alter pregnancy outcome by adjusting progesterone treatment at mid-luteal phase: a randomized controlled trial.

Our study aimed to determine whether mid-luteal serum P concentrations can serve as a predictive factor for in vitro fertilization (IVF) outcomes and whether increasing P dosage for patients with low levels at mid-luteal phase may improve pregnancy rates. It was a prospective, randomized controlled study. A total of 146 patients undergoing IVF treatment were prospectively enrolled and received routine luteal phase support (LPS) regimen of Endometrin® (progesterone) 200 mg/day. Serum P levels were measured 7 days after embryo transfer (ET). Considering a cutoff level of 15 ng/ml on this day, patients with higher levels continued the same dosage until pregnancy test (control group). Patients with lower levels were randomly allocated to continue Endometrin® 200 mg/day (Group A) or to increase Endometrin® dosage to 300 mg/day (Group B). The Main Outcome Measures were pregnancy rates. Both biochemical and clinical pregnancy and live birth rates were comparable between all groups regardless of P level on day 7 of luteal phase and regardless of dose adjustment. ROC analysis determined that mid-luteal P levels of 17 ng/ml can be a better predictor of cycle outcome. In conclusion raising the P dose at mid-luteal phase to 300 mg daily did not improve cycle outcomes.