Female age is associated with the optimal number of oocytes to maximize fresh live birth rates: an analysis of 256,643 fresh ART cycles

Research questionWhat is the optimal number of oocytes retrieved at which maximum live birth rate is observed after fresh autologous assisted reproductive technology (ART) cycles for women of different ages?DesignRetrospective cohort study of all fresh autologous ART aspiration cycles (n = 256,643) undertaken in Australia and New Zealand between 2009 and 2015. Primary outcome measure was live birth rate (LBR) (delivery of at least one liveborn baby at 20 weeks’ gestation or over per fresh aspiration cycle). Cycles were grouped according to female age (<30, 30–34, 35–49, 40–44 and ≥45 years) and ovarian response (one to three, four to nine, 10–14, 15–19, 20–25 and ≥25 oocytes). Secondary outcome was incidence of ovarian hyperstimulation syndrome (OHSS) requiring hospitalization.ResultsAt different oocyte yields, LBR per fresh aspiration cycle peaked and then declined at, depending on female age: <30 years: six to 11 oocytes (LBR 31–34%); 30–34 years: 11–16 oocytes (LBR 29–30%); 35–39 years: nine to 17 oocytes (LBR 21–24%); and 40–44 years: 15–17 oocytes (LBR 11–12%). The incidence of OHSS increased significantly with the number of oocytes retrieved, from 1.2% with 15 oocytes retrieved to 9.3% with 30 or more oocytes retrieved (P < 0.001).ConclusionThe optimal number of oocytes at which maximum LBR was observed in a fresh aspiration cycle was highly dependent on age. Because of the observational nature of the results, a cause–effect relationship between the number of oocytes retrieved and LBR should not be assumed; evidence from well-designed randomized control trials is required before clinical advice can be suggested.     

Is early initiation of infertility treatment justified in women over the age of 35 years?

Research questionNatural fecundity and the success of IVF and intracytoplasmic sperm injection (ICSI) rate both decrease with age. For this reason, in women older than 35 years, it is generally recommended to start the infertility work-up after only 6 months. This assumption, however, may expose couples to over-diagnosis and over-treatment.DesignA theoretical model aimed at assessing the effects of starting the infertility work-up after 6 rather than 12 months of trying to conceive naturally was developed. The assumptions of the model were as follows: infertile women are treated with IVF/ICSI for up to three cycles; IVF/ICSI success rate at first cycle linearly declines with age (3% per year between the ages of 35 and 45 years); the drop-out rate after the first and second cycle is 18% and 25%, respectively; the relative reduction of the success rate at second and third cycle is 16% and 26%, respectively.ResultsEarly initiation of treatment moderately improved the cumulative chances of live birth resulting from a full IVF/ICSI programme. This improvement is dependent on age. Specifically, it increased from 2.0% at age 35 years to 3.0% at age 43 years. Conversely, the incremental success rate per single IVF cycle was mainly stable, varying only from 1.4% at age 35 years to 1.3% at age 43 years.ConclusionsIn women older than 35 years, early initiation of the infertility work-up is associated with only a modest increase in the rate of success of IVF/ICSI. In most scenarios, this advantage may compare unfavourably with the chances of natural conception during the 6-month period.     

Association between the number of oocytes retrieved and cumulative live birth rate in women aged 35–40 years undergoing long GnRH agonist IVF/ICSI cycles

Purpose

To study the association between the numbers of oocytes retrieved and the cumulative live birth rates (LBR) in women aged 35–40 years undergoing long GnRH agonist IVF/ICSI cycles.

Methods

A total of 931 women aged 35–40 years who underwent their first cycle of IVF/ICSI treatment between January 2010 and December 2013 at Nanjing Drum Tower Hospital were identified and reviewed. The main endpoint of this study was the cumulative LBR after one complete oocyte retrieval, which included fresh and all subsequent frozen–thaw embryo transfer cycles. Odds ratios (OR) and 95% confidence interval (CI) for live birth were estimated by multivariate logistic regression analysis. Furthermore, all the women were divided into four groups based on the number of oocytes retrieved: 0–4, 5–9, 10–14 or ≥15 oocytes group. Variables were then compared among groups.

Results

We found that 634 out of the 931 patients (68.1%) achieved at least one live birth. The number of oocytes retrieved was an independent predictive factor for live birth, with OR 1.20 (95% CI 1.15–1.26) when adjusted for age (years), duration of infertility and Gn (gonadotrophin) doses. The cumulative LBR in the four different oocyte groups was 35.6, 68.8, 83.4 and 89.2%, respectively. When the 1–4 oocytes group was issued as a reference, the ORs for cumulative LBR gradually increased to 3.66, 6.74 and 11.77 in other three oocytes groups, respectively. The moderate–severe ovarian hyperstimulation syndrome (OHSS) rate was dramatically increased in the ≥15 oocytes group (6.9%) when compared to that in the 10–14 oocytes group (0.8%), while the cumulative LBR only increased 5.8% (from 83.4 to 89.2%).

Conclusions

The ideal number of oocytes retrieved in women aged 35–40 years is 10–14 oocytes, which achieves a high cumulative LBR while maintaining an acceptable low OHSS rate.

     

Collecting semen samples at home for IVF/ICSI does not negatively affect the outcome of the fresh cycle

Research questionDoes the site of semen collection influence IVF/intracytoplasmic sperm injection (ICSI) cycle outcome?DesignRetrospective study performed at the University Medical Centre Ljubljana, including all stimulated and modified natural IVF/ICSI cycles (with at least one oocyte retrieved) performed in 2019 with fresh ejaculated semen samples. IVF/ICSI cycle outcomes, in terms of oocytes, embryos and pregnancy rates according to site of semen sample collection (at home or at clinic) were evaluated.ResultsSamples collected at clinic had significantly lower sperm concentration (median [interquartile range, IQR], 50 [20–100] million/ml versus 70 [30–100] million/ml, adjusted odds ratio [OR] 0.001, 95% confidence interval [CI] 1.574  ×  10^–6 to 0.196, P = 0.012) and motility (60 [50–70]% versus 70 [50–70]%, adjusted OR 0.034, 95% CI 0.002 to 0.563, P = 0.018, adjusted for age). There was no difference in total sperm count, semen volume or sperm morphology, or women's age (36 [32–39] versus 36 [33–39] years) and men's age (37 [34–41] versus 38 [34–42] years), between semen samples collected at clinic versus at home. When all IVF/ICSI cycles were analysed together using generalized estimating equation analysis, no significant difference in cycle outcomes attributed to site of semen sample collection was observed. There were also no significant differences in cycle outcomes when only first cycles were analysed.ConclusionsCollecting semen samples at home has a positive effect on sperm quality (sperm concentration and motility were higher), but no significant differences in cycle outcomes are observed when these samples are used in IVF/ICSI cycles. Therefore, it is suggested that collecting semen samples at home for IVF/ICSI procedures is safe and has no negative effect on treatment outcomes.     

The effect of the Ontario Fertility Program on IVF utilization and outcomes in women of advanced reproductive age

Research questionAre the demographics and clinical outcomes similar for patients aged ≥40 but <43 years seeking IVF in Ontario, Canada, before and after implementation of the Ontario Fertility Program (OFP), which supports public funding of IVF up to age 43?DesignRetrospective database review using the Canadian Assisted Reproductive Technologies Registry Plus (CARTR Plus) and Better Outcomes Registry & Network (BORN) Ontario databases. Cycles from women who underwent autologous IVF and who were aged ≥40 and <43 years were analysed during a 2-year period prior to (2014–2015) and after (2016–2017) introduction of publicly funded IVF through the OFP.ResultsThere was an almost doubling of treatment cycles in women aged 40–42 in Ontario after the OFP launch. Clinical pregnancy rate per cycle start (17.0% versus 13.3%, P < 0.001) and cumulative clinical pregnancy rate per stimulation cycle (20.5% versus 16.8%, P < 0.001) were statistically higher in women before OFP implementation. While cumulative live birth rate per cycle start was statistically lower after funding was introduced (12.5% versus 10.5%, P = 0.027), the clinical importance of this difference appears small. Outcomes were above the 10% live birth per cycle threshold recommended by the Advisory Process for Infertility Services panel, commissioned by the Ministry of Health, to determine access to publicly funded IVF.ConclusionsUse of IVF in women over age 40 doubled with access to OFP funding; however, eligibility criteria based on age still meet the target of achieving a cumulative live birth rate of at least 10%.     

Modified natural-cycle cryopreserved embryo transfer: is a washout period needed after a failed fresh cycle?

Research questionAre the characteristics of the natural cycle or modified natural cycle (mNC), or live birth rates (LBR), affected by delaying frozen embryo transfer (FET) after a failed fresh IVF cycle?DesignIn a retrospective study, conducted at a university-affiliated tertiary centre, 198 women aged 18–45 years undergoing their first FET cycle after a failed fresh embryo transfer attempt using an mNC were evaluated. Cycles were divided according to the time interval between oocyte retrieval and the start of the FET cycle into the immediate FET group (<22 days) and the delayed FET group (≥22 days). The main outcome measures were ovulation day and LBR.ResultsThe mean interval between oocyte retrieval and the start of the FET cycle was 15.6 ± 3.2 days in the immediate FET group and 84.8 ± 73.7 days in the delayed FET group (P < 0.001). Ovulation day was significantly delayed in the immediate FET group (day 17.1 ± 4.4 versus day 15.4 ± 3.7; P = 0.004). There was no difference between the immediate and delayed FET groups in terms of clinical pregnancy rate (CPR) (25.4% and 25.0%, respectively) or LBR (21.2% and 20.0%, respectively).ConclusionsNatural-cycle characteristics are similar in immediate and delayed cycles, except for a slight delay in ovulation day. Deferring mNC-FET after a failed fresh IVF cycle does not improve the reproductive outcome. These results should encourage patients and clinicians who want to proceed with FET immediately after failure of fresh IVF.     

Outcome of assisted reproductive technology in women over the age of 41

OBJECTIVE: To analyze the results of ongoing pregnancies and deliveries after assisted reproductive technology (ART) in women aged >/=41 years, stratified by year of age. DESIGN: Retrospective study. SETTING: University hospital, IVF unit. PATIENT(S): A total of 431 IVF and intracytoplasmic sperm injection (ICSI) cycles were initiated in women >/=41 years of age. INTERVENTION(S): Medical files of ART patients and pregnancy outcomes were reviewed. MAIN OUTCOME MEASURE(S): Oocytes retrieved, embryos developed, and clinical pregnancy and delivery rates. RESULT(S): Of the 431 started cycles, 376 (87%) reached the oocyte retrieval stage. The mean number of oocytes aspirated per patient was 5.4 +/- 0.9 and 6.7 +/- 1.2 in the IVF and ICSI cycles, respectively, and the number of embryos obtained was 2.3 +/- 1.3 and 2.8 +/- 1.6 in the IVF and ICSI cycles, respectively. The number of transferable embryos was 2.0 +/- 1.2 and 2.5 +/- 0.8. The pregnancy rate per oocyte pickup (OPU) was 12.4%; however, the delivery rate per OPU was 4.5%. The mean delivery rate per OPU among women aged 41-43 years was 2%-7%. There were no deliveries aged >/=44 years and no pregnancies at the age of 45 years. The pregnancy and delivery rates of the ICSI and IVF patients were similar after stratification by age. CONCLUSION(S): In our studies, ART performed with homologous oocytes, whether by IVF or ICSI, yielded no clinical pregnancies among women aged >/=45 years and no deliveries aged >/=44 years. The mean delivery rate per oocyte retrieval among women aged 41-43 years varied between 2% and 7%.     

Maternal age over 40 years and pregnancy outcome: a hospital-based survey

Objective: Increased risk for adverse pregnancy outcomes with advancing maternal age has been described but the strength of association remains debated, particularly in presence of confounding factors such as parity, twin pregnancy and pregnancy from assisted reproductive technologies. The aim of this study was to evaluate pregnancy outcomes in a large cohort of women aged over 40 years. The hypothesis was that advanced maternal age may be an independent risk factor for adverse pregnancy outcome.

Study design: We reviewed the clinical records of 56,211 women who delivered at Sant’Anna University Hospital, Turin, Italy, in the period between 2009 and 2015. Of these, 3798 women aged over 40 years were divided into two age groups (40???44 years and ≥45 years). Women of any parity, with singleton or twin pregnancies, or with assisted reproductive technology pregnancies were included. Women aged less than 40 years were considered as controls. Primary outcome measures were maternal and perinatal complications. Comparisons were performed using Chi-square test and Fisher’s exact test. Univariate analysis and logistic regression analysis were performed to test the possible independent role of maternal age as a risk factor for adverse pregnancy outcome.

Results: Maternal age was an independent risk factor for gestational diabetes (age 40–44 years: odds ratios (OR) 2.10, 95% CI 1.80–2.45; age ≥45 years: OR 2.83, 95% CI 1.79–4.46) and early-onset preeclampsia (age 40–44 years: OR 2.10, 95% CI 1.63–2.70; age ≥45 years: OR 3.16, 95% CI 1.68–5.94). The risk for placenta praevia was higher in the women aged 40–44 years (OR 1.87, 95% CI 1.36–2.57). Neonatal outcomes were similar among groups, except for the rate of birth weight less than 2500?g, which was higher in women aged 40–44 years (OR 1.27, 95% CI 1.12–1.42). However, older women showed an overall higher incidence of preterm birth.

Conclusions: Maternal age over 40 years is an independent risk factor for adverse pregnancy outcomes, particularly for the mother. Pregnancies in women over 40 years should be considered at risk and carefully monitored with individualized care protocols.     

Reproductive outcome of women 43 years and beyond undergoing ART treatment with their own oocytes in two Connecticut university programs

Purpose

The aim of this study was to analyze the outcomes of IVF/ICSI cycles in women aged 43 and beyond.

Methods

Retrospective analysis of clinical pregnancy and live birth rates in168 fresh, non donor, ART cycles performed in two Connecticut university IVF programs.

Results

In women of 43 and 44 years the overall clinical pregnancy and live birth rates were 8.3 % and 5.3 % per initiated cycle, respectively. There were no clinical pregnancies in women ≥45 years old. First cycle characteristics were not different from repeated cycles in terms of duration of ovulation induction, number of collected oocytes and transferred embryos (p > 0.05).

Conclusions

Pregnancies can still be achieved with IVF/ICSI up to the age of 44. Since most pregnancies occurred within the first 3 cycles, another attempt may be a reasonable option before resorting to oocyte donation for patients who failed two previous cycles. Women 45 years and beyond do not benefit from ART procedures using their own oocytes.     

Live birth rates remain stable in modified natural IVF despite low anti-Müllerian hormone: analysis of 638 cycles

Research questionDo live birth rates (LBR) following modified natural IVF (mnIVF) differ according to serum anti-Müllerian hormone (AMH) concentration?DesignRetrospective cohort study including 638 women aged ≤39 years starting their first mnIVF cycle at a university-affiliated private IVF centre. Patients were divided into three groups, by concentration of AMH: ≤0.5 ng/ml (25th percentile), 0.51–2.03 ng/ml (25–75th percentile, reference) and 2.04–6.56 ng/ml (75th percentile). Analyses were stratified by AMH percentile and the age of patients (<35, 35–39 years). Logistic regression assessed the impact of age and AMH percentile on outcomes. LBR was the primary outcome measure.ResultsLBR per started cycle were comparable across AMH percentiles (11.6%, 12.4% and 17.0% for the 25th, 25–75th and 75th percentile, respectively). No statistically significant difference was found between the three AMH groups with respect to cancellation, successful egg retrieval, embryo transfer, or biochemical and clinical pregnancy rates. Logistic regression analysis did not identify AMH percentile as a significant predictor of live birth. Compared with the reference group, the odds ratios (OR [95% confidence interval, CI]) for live birth in the <25th and >75th AMH percentile groups were 0.97 (0.54–1.76) and 1.41 (0.82–2.41), respectively. The results were the same regardless of age group (<35 years, 35–39 years).ConclusionsSerum AMH cannot be used to predict mnIVF outcomes. Patients in lower/upper AMH percentiles showed pregnancy and LBR comparable to patients with normal AMH.     

Both high and low HCG day progesterone concentrations negatively affect live birth rates in IVF/ICSI cycles

Research questionCan previous reports of a decreased probability of success in stimulated IVF cycles with premature rise of progesterone, as determined by progesterone concentration on HCG day (PHCG), be confirmed?DesignRetrospective, observational, single-centre cohort study conducted on 5447 IVF and intracytoplasmic (ICSI) cycles carried out among 2192 patients between 2009 and 2015, with conventional ovarian stimulation. This large database was used to develop a non-linear mixed prognosis model of live birth rate (LBR) incorporating PHCG as a predictor.ResultsIn addition to known predictors (age, body mass index, anti-Müllerian hormone, type of infertility), PHCG was associated with a linear effect (OR 0.78 per Log[PHCG]ng/ml, 95% CI 0.611 to 0.997, P = 0.047) combined with a strong quadratic effect (OR 0.585 per Log²(PHCG)ng/ml, 95% CI 0.444 to 0.775, P < 0.001) resulting into a parabolic reverse-U curve. A significant interaction (P = 0.038) was found between PHCG and number of oocytes if three or less, but the effect of PHCG remains modest. For higher oocyte numbers, LBR rapidly increases with number of retrieved oocytes; however, LBR becomes more sensitive to PHCG as the number of oocytes increases. Higher live birth prognoses occur for optimal PHCG but are sharply reduced for lower or higher PHCG.ConclusionsEvidence is provided of an important negative effect of PHCG at lower and higher values, independent of oocyte number, thus defining appropriate ranges for fresh embryo transfer or freeze-all strategy. In poor responders, premature progesterone rise may be ignored, thus avoiding unnecessary cancellations or embryo freezing. Conversely, in higher responders, the negative effect of progesterone elevation is more pronounced, suggesting that freeze-all policy should be applied more widely.     

Cumulative live birth rate of advanced-age women more than 40 with or without poor ovarian response

Objective

The aim of this study was to investigate cumulative live birth rate (CLBR) per oocyte retrieval cycle and per patient in women over 40 years old undergoing IVF/ICSI treatments, stratified for age, ovarian response and oocyte retrieval cycle number.

High concentration of first-measured HCG after embryo transfer is associated with subsequent development of pre-eclampsia

Research questionAre outlier high values of first-measured human chorionic gonadotrophin (HCG) following embryo transfer related to pregnancy complications, specifically pre-eclampsia?DesignThis retrospective cohort study screened 3448 women aged 18–45 years who underwent IVF between 2014 and 2019 and evaluated 614 women who had an intrauterine pregnancy following single embryo transfer (SET), 423 of whom had a live birth. Pregnancy and birth outcome information was available for final analysis in 280 cases. The setting was a university-based IVF centre. HCG was measured at a standardized time after the embryo transfer and the values correlated with adverse pregnancy outcomes associated with poor placentation.ResultsWomen with first-measured HCG in the highest quintile had a higher incidence of pre-eclampsia than those with lower HCG concentrations (odds ratio [OR] 4.08, 95% confidence interval [CI] 1.41–11.82) even after controlling for age, body mass index, parity and type of embryo transfer. Additionally controlling for embryo stage at embryo transfer did not change the results (OR 3.97, 95% CI 1.37–11.46). No differences were found in the incidence of fetal growth restriction.ConclusionsThis is the first known report that links high first-measured HCG after SET to an adverse pregnancy outcome. If confirmed by future studies, initiation of preventive interventions at a very early stage of pregnancy merits further evaluation in this cohort of patients.     

A short length of gonadotropin hyperstimulation is sufficient to achieve an optimal IVF outcome in advance-aged women

ObjectiveTo analyze the duration of gonadotropin hyperstimulation's impacts on oocyte quality and clinical outcomes in aged in vitro fertilization (IVF) patients.Materials and methodsThis retrospective study was carried out using IVF records of the Chang Gung Memorial Hospital IVF center from January 2017 to December 2019. A total of 308 IVF cycles with patients aged 40–44 years were included. Clinical characteristics of patients who received a short controlled ovarian hyperstimulation (COH) (i.e., 6–7 days; s-COH group) or a long COH treatment (i.e., 9–10 days; l-COH group) were compared. In addition, analysis was conducted using data within two age subgroups: 40–42 years and 42–44 years subgroups.ResultsThe s-COH group received significantly lower total doses of gonadotropin and had smaller leading follicles at the time of ovulation trigger when compared to the l-COH group. The s-COH group also produced a significantly lower number of oocytes, mature metaphase II (MII) oocytes, and 2 PN zygotes compared to the l-COH group. However, there was no significant difference in the number of transferable and good-quality embryos between the two treatment groups. Likewise, the pregnancy rate and live birth rate were comparable in the s-COH and l-COH groups. Similar results were obtained when the analysis was limited to select age subgroups (i.e., 40–42 and 42–44 years subgroups).ConclusionWhile a long COH generates more oocytes per cycle, a 6–7 days COH treatment, which is at the lower end of the recommended window of stimulation, could achieve a pregnancy outcome comparable to that applied 9–10 days of COH in aged patients.     

Effect of metformin taken in the ‘fresh’ in vitro fertilization/intracytoplasmic sperm injection cycle upon subsequent frozen embryo replacement in women with polycystic ovary syndrome

Objective.?We aimed to determine whether metformin when taken during a fresh in?vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle affects live birth rate (LBR) in subsequent frozen embryo replacement cycles (FERC).

Design. A retrospective database analysis of women with polycystic ovary syndrome (PCOS) undergoing FERC at a university teaching hospital between 2002 and 2007 (n?=?142). The outcome of FERC in women who had taken metformin in the ‘fresh’ IVF/ICSI cycle (group A, n?=?28) and those who had not (group B, n?=?114) were compared.

Results.?In the first FERC there was a significantly higher LBR (A?=?28.6%, B?=?12.3%, OR 2.86 95% CI 1.06–7.71). Women who had elective cryopreservation due to ovarian hyperstimulation syndrome risk were found to have significantly higher LBRs if metformin was taken in the fresh IVF/ICSI cycle (A?=?44.4%, B?=?7.9%, OR 9.33 95% CI 1.60–54.58).

Conclusions.?Women with PCOS who take metformin during IVF/ICSI may have a higher LBR in subsequent FERC, especially in those who have elective cryopreservation for OHSS risk. The findings of this study are limited by its retrospective design and small sample size and require confirmation in an adequately powered prospective randomized controlled trial.     

Pregnancy Rates After Surgical Treatment of Deep Infiltrating Endometriosis in Infertile Patients With at Least 2 Previous In Vitro Fertilization or Intracytoplasmic Sperm Injection Failures

Study ObjectiveTo assess the postoperative probabilities of pregnancy in patients with deep infiltrating endometriosis (DIE) and ≥2 previous in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) failures.DesignRetrospective study using data prospectively recorded in the North-West Inter Regional Female Cohort for Patients with Endometriosis (CIRENDO) database.SettingUniversity tertiary referral center.PatientsInfertile patients under the age of 43 years, having undergone ≥2 previous IVF or ICSI failures, who were surgically managed for DIE.InterventionsComplete excision of DIE.Measurements and Main ResultsThe pregnancy rate after surgery was assessed. One hundred and four infertile patients had surgery in 7 different centers participating in the database. Seventy-seven women intended to get pregnant postoperatively. Four patients who got pregnant by oocyte donation were excluded, resulting in a sample of 73 women. The mean patient age was 31.9 years (standard deviation [SD], 4.1), and the mean length of history of infertility was 48.4 months (SD, 26.5). Stage III and IV endometriosis were recorded in 83.6% of patients. The mean postoperative follow-up was 46.6 months (SD, 20.5). The postoperative pregnancy rate was 43.8% with a mean time from surgery to pregnancy of 11.1 months. 21.8% of pregnancies were spontaneous, 31.2% were obtained by IVF, 21.8% by frozen embryo transfer, 18.7% by IVF-ICSI, and 3.1% by intrauterine insemination. Multivariate analysis revealed that ovarian surgery, age ≥35 years old, and stage II endometriosis was associated with the probability of conception.ConclusionInfertile women with ≥2 IVF-ICSI failures may be referred for surgery as it appears related to reasonable postoperative pregnancy rates, particularly when endometriomas surgery is either not required or not performed. Surgery for DIE does not routinely delay conception, as it usually occurs during the year following surgery.     

Comparison of in vitro fertilisation/intracytoplasmic sperm injection on live birth rates in couples with non-male factor infertility and advanced maternal age

PurposeTo determine if the use of ICSI in women of advanced maternal age with non-male factor infertility increases chances of live birth.MethodsRetrospective data analysis of 10 years of cycle data from a single Australian IVF clinic (Repromed). First cycle patients only of an advanced maternal age (≥ 35 years) with non-male factor infertility utilising standard IVF or ICSI insemination and having at least three oocytes collected at egg pick up were assessed for live birth following transfer of single genetically unscreened blastocyst (N = 577). Subanalysis of clinical pregnancy, miscarriage, fertilisation, embryo utilisation rate and having a blastocyst for transfer were considered. Unadjusted, covariate adjusted and propensity score weighted analysis were performed.ResultsThe use of standard IVF insemination in women ≥ 35 years with non-male factor infertility increased the chance of a live birth compared with ICSI insemination (unadjusted OR = 2.72, 95% CI [1.78, 4.17]; adjusted OR = 2.64, 95% CI [1.64, 4.27] and weighted OR = 2.26, 95% CI [1.72, 2.98] 31% vs 14%). All other outcomes (fertilisation rate, embryo utilisation, blastocyst for embryo transfer and miscarriage rate) were unaffected.ConclusionIn couples with advanced maternal age and non-male factor infertility, standard IVF insemination appears to increase the chance of a live birth compared with ICSI. As such, the results of this study support the use of routine IVF as the preferred insemination technique for older women in non-male factor infertility. However, future randomised controlled trials are still required to assess this policy.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10815-020-02026-8.     

Monozygotic twinning after in vitro fertilization/intracytoplasmic sperm injection treatment is not related to advanced maternal age,intracytoplasmic sperm injection,assisted hatching,or blastocyst transfer

ObjectiveTo evaluate the effect of assisted reproductive techniques on the incidence of monozygotic twins (MZT) and the associated pregnancy outcomes.Materials and methodsThis was a retrospective study of all in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles with MZT pregnancies in our center from January 2001 to December 2011. The diagnosis of MZT pregnancies with their respective placental configurations was based on the results of ultrasonographic examinations performed during either the first or second trimester. The treatment characteristics and outcomes of each IVF cycle were recorded and stored in a computer database.ResultsA total of 17 cycles with MZT pregnancies were identified, resulting in an overall incidence of MZT of 1.3%. The incidence of MZT for women aged <35 years and ≥35 years were 1.5% and 0.8%, respectively (p = 0.319). The incidence was not significantly different between ICSI and non-ICSI cycles (1.4% vs. 1.0%; p = 0.620). In addition, the incidence was not increased in the assisted hatching (AH) group compared to those without AH (0.9% vs. 2.1%; p = 0.103). Finally, cycles with embryo transfer at the blastocyst stage had an MZT incidence that was not significantly different from those transferred at the cleavage stage (1.4% vs. 1.3%, respectively; p = 1.000). The incidence of each type of chorionicity, dichorionic–diamniotic, monochorionic–diamniotic, and monochorionic–monoamniotic, was 33.3%, 46.7%, and 20.0%, respectively. A total of 11 of 39 (28%) monozygotic babies and 16 of 19 (84%) coexisting heterozygotic babies were born alive.ConclusionUntil definite conclusions are drawn from larger trials, patients receiving IVF should not be overly concerned about the increase in MZT risk when proceeding to various assisted reproductive procedures (i.e., ICSI, AH, and blastocyst transfer). However, there is some evidence that the incidence of monochorionic–monoamniotic twins may be significantly increased after IVF/ICSI cycles. Patients should be informed about the possible obstetric complications regarding this rare type of MZT.     

The BlastGen study: a randomized controlled trial of blastocyst media supplemented with granulocyte–macrophage colony-stimulating factor

Research questionDoes Embryogen®/BlastGen™ culture medium improve live birth rates compared with standard culture medium for women undergoing IVF and intracytoplasmic sperm injection (ICSI) with poor prognosis.DesignRandomized clinical trial. A total of 100 couples undergoing IVF/ICSI were randomly allocated to having their inseminated oocytes incubated in either Embryogen®/BlastGen™ sequential culture media or standard Cleavage/Blastocyst sequential culture media for 5 days (ClinicalTrials.gov Identifier: NCT02305420).ResultsNo statistically significant difference in live birth rate was found between the control group and the Embryogen®/BlastGen™ group (17 [34%] versus 11 [22%], respectively) (OR 0.55; 95% CI 0.22 to 1.32; P = 0.18). After adjustment for maternal age, body mass index and fertilization procedure, the blastulation rate reduced (40.6 ± 26.5 versus 24.6 ± 26.7; RR 0.70, CI 0.52 to 0.95; P < 0.05), and grade of the embryo transferred (OR 0.35, CI 0.16 to 0.77; P < 0.01) when Embryogen®/BlastGen™ medium was used.ConclusionA significant reduction in day-5 embryo outcome parameters was found using Embryogen®/BlastGen™ compared with standard medium, and insufficient evidence of a difference in pregnancy outcomes. Taking into consideration the small samples size, study limitations and strict inclusion criteria of this single-centre study, further research is needed to determine the efficacy of Embryogen®/BlastGen™ medium in couples undergoing IVF/ICSI.     

Oocyte competence is independent of the ovulation trigger adopted: a large observational study in a setting that entails vitrified-warmed single euploid blastocyst transfer

Purpose

To assess whether the GnRH-agonist or urinary-hCG ovulation triggers affect oocyte competence in a setting entailing vitrified-warmed euploid blastocyst transfer.

Methods

Observational study (April 2013–July 2018) including 2104 patients (1015 and 1089 in the GnRH-a and u-hCG group, respectively) collecting ≥1 cumulus-oocyte-complex (COC) and undergoing ICSI with ejaculated sperm, blastocyst culture, trophectoderm biopsy, comprehensive-chromosome-testing, and vitrified-warmed transfers at a private clinic. The primary outcome measure was the euploid-blastocyst-rate per inseminated oocytes. The secondary outcome measure was the maturation-rate per COCs. Also, the live-birth-rate (LBR) per transfer and the cumulative-live-birth-delivery-rate (CLBdR) among completed cycles were investigated. All data were adjusted for confounders.

Results

The generalized-linear-model adjusted for maternal age highlighted no difference in the mean euploid-blastocyst-rate per inseminated oocytes in either group. The LBR per transfer was similar: 44% (n=403/915) and 46% (n=280/608) in GnRH-a and hCG, respectively. On the other hand, a difference was reported regarding the CLBdR per oocyte retrieval among completed cycles, with 42% (n=374/898) and 25% (n=258/1034) in the GnRh-a and u-hCG groups, respectively. Nevertheless, this variance was due to a lower maternal age and higher number of inseminated oocytes in the GnRH-a group, and not imputable to the ovulation trigger itself (multivariate-OR=1.3, 95%CI: 0.9–1.6, adjusted p-value=0.1).

Conclusion

GnRH-a trigger is a valid alternative to u-hCG in freeze-all cycles, not only for patients at high risk for OHSS. Such strategy might increase the safety and flexibility of controlled-ovarian-stimulation with no impact on oocyte competence and IVF efficacy.