Time-lapse variables and embryo gender: a retrospective analysis of 81 live births obtained following minimal stimulation and single embryo transfer

Purpose

The purpose of this study was to determine which morphokinetic variables are related to embryo gender in a cohort of consecutive live births obtained through single blastocyst transfer following mild ovarian stimulation.

Methods

Eighty-one live births (49 % of them females) from successfully treated, consecutive infertile patients (maternal age 36.9?±?3.8 years, range 28–46) who underwent minimal ovarian stimulation, prolonged embryo culture in a time-lapse monitoring (TLM) incubator and elective single blastocyst transfers during 2012–2014. Early (PNf, t2–t9, cc2a, b, s2, s3) and late (tM, tSB, tfullB, texpB₁, and texpB₂) morphokinetic variables were scored according to published consensus criteria and were normalized to the time of pronuclear fading. For each variable, the ranges with the highest proportion of female embryos (optimal range) were determined by detailed examination of histograms.

Results

Female embryo gender was associated both with late cleavage (t8), morula (tM), and blastocyst stage morphokinetic variables. The strongest associations (adjusted ORs, 7.0–7.8) were found for late, expanded stage blastocyst parameters; tfullB, texpB₁, and texpB₂. The proportion of female embryos was 69–71 and 25–26 % inside and outside of the optimal ranges, respectively. This allowed to predict 74–78 % of them, increasing their proportion by 57 % compared to the average.

Conclusions

Although the sample size of our cohort was limited, our findings suggest that several expanded blastocyst stage morphokinetic parameters are associated with female embryo gender. If confirmed on a larger sample these could be potentially used to increase the proportion of female embryos among non-invasively selected blastocysts following single embryo transfer.

     

Complications related to ovarian stimulation and oocyte retrieval in 4052 oocyte donor cycles

A retrospective study was conducted in a private infertility centre to evaluate the rate of complications in a large oocyte donation programme. A total of 4052 oocyte retrievals were performed between January 2001 and October 2007. Altogether, 1238 cycles (30.6%) were stimulated with the use of gonadotrophin-releasing hormone (GnRH) agonists and in 2814 cycles (69.4%) the GnRH antagonist protocol was used. The GnRH antagonist treated cycles were triggered with human chorionic gonadotrophin (HCG) or a GnRH agonist in 1295 and 1519 cycles, respectively. Complications related to oocyte retrieval occurred in 17 patients (0.42%) (intra-abdominal bleeding: n = 14, severe pain: n = 2, ovarian torsion: n = 1). Fourteen of these were hospitalized (0.35%) and six donors (0.15%) required surgical intervention. Pelvic infections, injury to pelvic structures or anaesthesiological complications were not observed in this series. Moderate/severe ovarian hyperstimulation syndrome (OHSS) occurred in 22 donors; 11 required hospital admission and 11 were managed on an outpatient basis. All cases were related to HCG triggering (0.87%). Serious complications related to oocyte retrieval occurred at a low rate in healthy young donors. The risk of OHSS can be substantially reduced by specific stimulation protocols, which include GnRH agonist triggering. Prospective oocyte donors should be adequately counselled about the risks related to egg donation.     

Triggering with HCG or GnRH agonist in GnRH antagonist treated oocyte donation cycles: a randomised clinical trial

Aim.?To compare donor and recipient outcome after inducing the final oocyte maturation with hCG or GnRH agonist in GnRH-antagonist treated oocyte donation (OD) cycles.

Methods.?Two-hundred fifty-seven oocyte donors were enrolled to participate in a clinical trial in a private fertility centre. After stimulation with 225 IU rFSH and Cetrorelix 0.25 mg/day, 212 oocyte donors were randomised with sealed envelopes for triggering with recombinant hCG (Ovitrelle 250 μgr, n = 106) or a GnRH agonist (triptorelin 0.2 mg, n = 106).

Results.?The number of retrieved COCs (12 ± 6.3 vs 11.4 ± 6.4), mature oocytes (8 ± 4.6 vs 7.5 ± 4.1), the proportion of mature oocytes (67.2 ± 20.4% vs 67.1 ± 20.9%) and fertilisation rates (67.8 ± 23.5% vs 71.1 ± 22.1%) were comparable. Clinical, ongoing pregnancy and live birth rates were not statistically different in the corresponding recipient groups. Nine cases of mild and one case of severe OHSS occurred in hCG group, whereas no cases were detected in GnRH agonist group.

Conclusions.?The findings of our RCT suggest that donor and recipient outcome are comparable in OD cycles triggered with hCG or a GnRH agonist. Furthermore, the risk of OHSS seems to be reduced considerably, therefore the combination of a GnRH antagonist protocol with GnRH agonist triggering constitutes a safe treatment option for egg-donors.     

Blastocyst culture is associated with an elevated incidence of monozygotic twinning after single embryo transfer

In a 7-year (2002-2008) retrospective study of a large IVF program based on minimal ovarian stimulation and single ET (47,841 single ETs), monozygotic twinning occurred in 1.01% of 14,956 clinical pregnancies. Blastocyst culture was associated with a significantly increased monozygotic twinning risk (adjusted odds ratio, 2.04; 95% confidence interval, 1.29-4.48), whereas embryo freezing, type of stimulation protocol used, intracytoplasmic sperm injection fertilization, or zona removal did not influence its incidence.     

Comparison between a GnRH antagonist and a GnRH agonist flare-up protocol in oocyte donors: a randomized clinical trial

BACKGROUND: Little information is available on the outcome of controlled ovarian hyperstimulation (COH) using GnRH antagonist in oocyte donation cycles especially in comparison with the short GnRH agonist protocol. This study was aimed at comparing the two stimulation protocols in oocyte donation (OD) cycles. METHODS: A total of 113 donors randomly received COH using either GnRH antagonist or GnRH agonist. The primary endpoint was the mean number of mature oocytes retrieved per started donor cycle. Secondary endpoints were the mean number of cumulus-oocyte-complexes (COCs) retrieved, the mean proportion of mature oocytes, pregnancy and implantation rates in recipients. RESULTS: Oocytes were distributed to 166 recipients. The mean number (+/- SD) of COC (11.6 +/- 5.8 versus 12.1 +/- 6.7), mature oocytes (8.4 +/- 4.4 versus 8.9 +/- 5.3) and the proportion of mature oocytes (70.8 versus 75.7%) retrieved per started donor cycle were similar in the antagonist and agonist groups, respectively. The implantation rate (26.1 versus 30.1%), clinical (40.2 versus 45.6%) and ongoing pregnancy rate per recipient cycle (32.2 versus 37.9%) were comparable in antagonist and agonist protocols, respectively. CONCLUSIONS: Similar mean number of mature oocytes and comparable pregnancy rates are achieved after OD in which donors received COH using GnRH antagonist or short GnRH agonist protocols.     

Oocyte donation in patients with Turner's syndrome: a successful technique but with an accompanying high risk of hypertensive disorders during pregnancy

BACKGROUND: Few data are available on pregnancy rate and obstetrical outcome after oocyte donation in Turner's syndrome patients. We conducted a retrospective analysis on the outcome of this subgroup. METHODS: Thirty oocyte donation cycles with fresh embryo transfer were performed in 21 patients between 2001 and 2004. RESULTS: The mean (+/-SD) age of the recipients was 33.1+/-1.8 years. The median (range) number of transferred embryos per cycle was two (1-4). Seventeen pregnancies were obtained (57%), of which 12 were clinical (40%). The implantation rate and the ongoing pregnancy rate were 22% (15 out of 68) and 30% (nine out of 30), respectively. Premature delivery was observed in 50% (four out of eight) of the pregnancies and intrauterine growth retardation in 55.5% (five out of nine) of the fetuses. Hypertensive disorders occurred in five out of eight pregnancies (three pre-eclampsias). CONCLUSIONS: Turner's syndrome patients achieve acceptable pregnancy rates after oocyte donation. A high rate of pregnancy-associated hypertensive disorders was observed which have led to a high rate of prematurity and intrauterine growth restriction. Although the number of cases in this study is limited, these results call for the need for intensive surveillance of such pregnancies. In order to reduce the risk of hypertensive disorders induced by multiple pregnancies, single embryo transfer should be proposed.