B. Hodes-Wertz

Idiopathic recurrent miscarriage is caused mostly by aneuploid embryos.

OBJECTIVE To determine any beneficial effects of preimplantation genetic screening (PGS) of all chromosomes by array comparative genomic hybridization (aCGH), with either day 3 or blastocyst biopsy, for idiopathic recurrent pregnancy loss (RPL) patients compared with their expected loss rate. DESIGN Case series report. SETTING Multiple fertility centers. PATIENT(S) A total of 287 cycles of couples with idiopathic RPL (defined as two or more losses). INTERVENTION(S) PGS was done with day 3 biopsy (n = 193) or blastocyst biopsy (n = 94), followed by analysis with aCGH. MAIN OUTCOME MEASURE(S) Spontaneous abortion rate, euploidy rate. RESULT(S) A total of 2,282 embryos were analyzed, of which 35% were euploid and 60% were aneuploid. There were 181 embryo transfer cycles, of which 100 (55%) became pregnant with an implantation rate of 45% (136 sacs/299 replaced embryos) and 94 pregnancies (92%) were ongoing (past second trimester) or delivered. The miscarriage rate was found to be only 6.9% (7/102), compared with the expected rate of 33.5% in an RPL control population and 23.7% in an infertile control population. CONCLUSION(S) Current PGS results with aCGH indicate a significant decrease in the miscarriage rate of idiopathic RPL patients and high pregnancy rates. Furthermore, this suggests that idiopathic recurrent miscarriage is mostly caused by chromosomal abnormalities in embryos.

Why do euploid embryos miscarry? A case-control study comparing the rate of aneuploidy within presumed euploid embryos that resulted in miscarriage or live birth using next-generation sequencing

OBJECTIVE To determine whether undetected aneuploidy contributes to pregnancy loss after transfer of euploid embryos that have undergone array comparative genomic hybridization (aCGH). DESIGN Case-control study. SETTING University-based fertility center. PATIENT(S) Cases included 38 patients who underwent frozen euploid ET as determined by aCGH, resulting in miscarriage. Controls included 38 patients who underwent frozen euploid ET as determined by aCGH, resulting in a live birth. INTERVENTION(S) Next-generation sequencing (NGS) protocols were internally validated. Saved amplified DNA samples from the blastocyst trophectoderm biopsies previously diagnosed as euploid by aCGH were reanalyzed using NGS. Cytogenetic reports of the products of conception for 20 of the pregnancies resulting in miscarriage were available for comparison. MAIN OUTCOME MEASURE(S) The incidence of aneuploidy and mosaicism using NGS within embryos resulting in miscarriage and live birth. RESULT(S) Of euploid embryos analyzed by aCGH resulting in miscarriage, 31.6% were mosaic and 5.2% were polyploid by NGS. The rate of chromosomal abnormalities was significantly higher in embryos resulting in miscarriage (36.8%) than in those resulting in live births (15.8%). The rate of mosaicism was twice as high among embryos resulting in miscarriage than those resulting in live birth, but this was not statistically significant. Next-generation sequencing detected more cases of mosaicism than cytogenetic analysis of products of conception. CONCLUSION(S) Undetected aneuploidy may increase the risk of first trimester pregnancy loss. Next-generation sequencing may detect mosaicism and triploidy more frequently than aCGH, which could help to identify embryos at high risk of miscarriage. Mosaic embryos, however, should not be discarded as some can result in live births.

Baby budgeting: oocyte cryopreservation in women delaying reproduction can reduce cost per live birth.

OBJECTIVE To determine whether oocyte cryopreservation for deferred reproduction is cost effective per live birth using a model constructed from observed clinical practice. DESIGN Decision-tree mathematical model with sensitivity analyses. SETTING Not applicable. PATIENT(S) A simulated cohort of women wishing to delay childbearing until age 40 years. INTERVENTION(S) Not applicable. MAIN OUTCOME MEASURE(S) Cost per live birth. RESULT(S) Our primary model predicted that oocyte cryopreservation at age 35 years by women planning to defer pregnancy attempts until age 40 years would decrease cost per live birth from

Association of body mass index with embryonic aneuploidy

55,060 to

Retrospective analysis of outcomes following transfer of previously cryopreserved oocytes, pronuclear zygotes and supernumerary blastocysts

39,946 (and increase the odds of live birth from 42% to 62% by the end of the model), indicating that oocyte cryopreservation is a cost-effective strategy relative to forgoing it. If fresh autologous assisted reproductive technology (ART) was added at age 40 years, before thawing oocytes, 74% obtained a live birth, and cost per live birth increased to

Is Intracytoplasmic Sperm Injection Overused

61,887. Separate sensitivity analyses demonstrated that oocyte cryopreservation remained cost effective as long as performed before age 38 years, and more than 49% of those women not obtaining a spontaneously conceived live birth returned to thaw oocytes. CONCLUSION(S) In women who plan to delay childbearing until age 40 years, oocyte cryopreservation before 38 years of age reduces the cost to obtain a live birth.

Deliveries from trophectoderm biopsied, fresh and vitrified blastocysts derived from polar body biopsied, vitrified oocytes

OBJECTIVE To determine whether an association exists between body mass index (BMI) and embryo ploidy in patients undergoing in vitro fertilization (IVF) with trophectoderm biopsy and 24-chromosome preimplantation genetic screening (PGS). DESIGN Retrospective cohort study. SETTING University-based fertility center. PATIENT(S) 279 women aged 20-45 years with documented height and weight from the day of oocyte retrieval who underwent 24-chromosome PGS between 2010 and 2013. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) PRIMARY OUTCOMES number and percentage of euploid embryos. RESULT(S) Patients were grouped by World Health Organization (WHO) BMI class: underweight (<18.5, n = 11), normal weight (18.5-24.9, n = 196), overweight (25-29.9, n = 50), and obese (≥30, n = 22). Groups were similar by age (mean ± standard error of the mean: 37.5 ± 1.2 to 39.2 ± 0.9), ovarian reserve, and IVF cycle parameters. There was no difference in the number or percentage of euploid embryos by BMI category (<18.5: 27.6% ± 8.5; 18.5-24.9: 34.5% ± 2.2; 25-29.9: 32.1% ± 4.3; ≥30: 30.9% ± 7.3). Age was inversely related to euploidy, but adjusted multivariate regression models failed to demonstrate a statistically significant relationship between BMI and euploidy in underweight (adjusted odds ratio [AOR] 0.44; 95% confidence interval [CI], 0.09-2.10), overweight (AOR 0.90; 95% CI, 0.43-2.00), or obese (AOR 0.74; 95% CI, 0.25-2.20) patients compared with the normal-weight reference group. CONCLUSION(S) No statistically significant relationship was identified between BMI and euploidy in an otherwise homogenous cohort of patients undergoing IVF with PGS, suggesting that the negative impact of overweight and obesity on IVF and reproductive outcomes may not be related to aneuploidy.

Comment on: Gleicher N et al., 2016. Reprod biol endocrinol Sep 5;14(1)

Oocyte cryopreservation still bears the experimental label. Remarkable innovation in this field has led to immense improvement in clinical outcomes and has even resulted in outcomes comparable to those achieved following fresh embryo transfers. Such success has prompted this centre to investigate outcomes of cryopreservation options (oocyte versus pronuclear zygote versus supernumerary day-5 blastocyst after fresh embryo transfer). This study retrospectively analysed 200 cryopreservation cycles which were divided into three groups according to cryopreservation option, which were all cultured to blastocyst-stage post thaw/warming from January 2005 to December 2008, and compared them with 400 fresh embryo transfer cycles from the same time period. When compared with fresh embryo transfer, frozen embryo transfers originating from previously cryopreserved oocytes or pronuclear zygotes resulted in similar implantation, pregnancy and live-birth rates; however, frozen embryo transfers originating from supernumerary day-5 blastocysts resulted in lower outcomes. Thus, oocyte and/or pronuclear zygote cryopreservation appear to be the most viable options for women desiring fertility preservation. Cryopreservation of supernumerary blastocysts may lead to a slightly lower live-birth rate since the best-quality blastocysts are generally transferred during the fresh embryo transfer attempt.

Live Birth from Previously Vitrified Oocytes, After Trophectoderm Biopsy, Revitrification, and Transfer of a Euploid Blastocyst

PURPOSE We determined whether the use of intracytoplasmic sperm injection in couples who previously underwent intracytoplasmic sperm injection cycles elsewhere could be decreased without compromising the pregnancy rate. MATERIALS AND METHODS At our university in vitro fertilization-embryo transfer center we retrospectively analyzed the records of 149 fresh, in vitro fertilization-embryo transfer cycles in patients who underwent intracytoplasmic sperm injection elsewhere and subsequent fertilization by insemination only (all insemination group) or half insemination and half intracytoplasmic sperm injection at our center. We compared fertilization, implantation, clinical pregnancy and live birth rates. RESULTS The fertilization rate was 74% and 73% for the all insemination and the half intracytoplasmic sperm injection groups, respectively. In the latter group 69% of inseminated and 78% of intracytoplasmic sperm injected oocytes were fertilized. No cycle showed complete fertilization failure. No statistically significant difference in the live birth rate was found between the 2 groups. CONCLUSIONS More stringent criteria for intracytoplasmic sperm injection do not compromise the clinical outcome and reasonable fertilization can be achieved whether or not intracytoplasmic sperm injection is performed. Thus, although intracytoplasmic sperm injection is one of the greatest advances in our field, it is overused and should only be done for clinically proven indications.

Changing ovarian stimulation parameters in a subsequent cycle does not increase the number of euploid embryos

This longitudinal study reports preliminary findings of six patients who underwent first polar body biopsy followed by oocyte vitrification. All oocytes were warmed, inseminated by intracytoplasmic sperm injection and cultured to blastocyst. All suitable blastocysts underwent trophectoderm biopsy for aneuploidy screening, and supernumerary blastocysts were vitrified. Euploid blastocysts were transferred either fresh or in a subsequent programmed cycle. Of the 91 metaphase II oocytes, 30 had euploid first polar bodies. Development to blastocyst was more likely in oocytes with a euploid first polar body (66.7% versus 24.6%; P < 0.001). Nineteen euploid blastocysts were produced: 10 from oocytes with a euploid first polar body and nine from oocytes with an aneuploid first polar body. Five out of six patients (83%) had a live birth or ongoing pregnancy at the time of analysis. Eleven euploid blastocysts have been transferred and seven implanted (64%). Although the chromosomal status of the first polar body was poorly predictive of embryonic ploidy, an association was found between chromosomal status of the first polar body and development to blastocyst. Further study is required to characterize these relationships, but proof of concept is provided that twice biopsied, twice cryopreserved oocytes and embryos can lead to viable pregnancies.