Jonathan D. Kort

Fertility issues in cancer survivorship

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Microdose follicular flare: a viable alternative for normal-responding patients undergoing in vitro fertilization?

OBJECTIVE To compare cycle outcomes among normal-responding patients <or=30 years old receiving microdose follicular flare (MDF) and long-luteal agonist (LL). DESIGN Retrospective cohort study. SETTING Military-based assisted reproductive technology (ART) center. PATIENT(S) First autologous ART cycles among 499 women <or=30 years old from January 1999 to December 2005. INTERVENTION(S) After oral contraceptive pill (OCP) administration before cycle start, patients were nonrandomly assigned to either LL or MDF for LH surge suppression. Patients in the LL group received 1 mg/day leuprolide acetate (LA) on cycle day 21, which was reduced to 0.25 mg/day 10-14 days later. Patients in the MDF group received LA (40 microg twice a day) beginning 3 days after discontinuing OCPs. Both groups received a combination of hMG and recombinant FSH. MAIN OUTCOME MEASURE(S) Primary outcomes were implantation, clinical pregnancy, and live-birth rates; in-cycle variables included peak E(2), oocytes retrieved, oocyte maturity, and fertilization rate. RESULT(S) Multivariable models controlling for confounding by treatment indication found no significant differences between groups in implantation (MDF, 36%; LL, 38%), clinical pregnancy (MDF, 53%; LL, 56%), and live-birth rates (MDF, 47%; LL, 50%). No differences were observed in peak E(2), oocytes retrieved, oocyte maturity, fertilization rate, or embryos transferred. CONCLUSION(S) MDF use among normal-responding ART patients produced no differences in cycle outcome when compared with LL. Therefore, MDF may be a viable alternative for normal-responding patients.

Biomechanics and developmental potential of oocytes and embryos

The high incidence of multiple embryo transfers is evidence of the need for better methods of embryo selection. Additionally, methods to determine the reproductive competence of unfertilized oocytes are critically needed to inform the growing population of patients undergoing fertility preservation. The ideal method of oocyte and embryo selection would be noninvasive, inexpensive, and able to be incorporated into embryology workflow with minimal disruption. Methods to assess the biomechanical properties of cells offer many of these traits, and there is a growing body of evidence in multiple cell types demonstrating the biomechanical properties of cells are reflective of a cells intrinsic health. The associations with these properties are not mere coincidence, as many of the biomechanical properties are critical to cellular function. The biomechanical properties of oocytes and embryos undergo a dynamic, characteristic transformation from oocyte maturation through blastocyst formation, lending itself to biomechanical assessment. Many of the assessments made by embryologists, from ease of microinjection during intracytoplasmic sperm injection to degree of blastocyst expansion, are direct proxies for cellular biomechanics. Newer, objective and quantitative methods of biomechanical assessment are being applied to oocyte and embryo selection, with early use supporting their application in assisted reproduction.

Caution: counseling patients with diminished ovarian reserve and recurrent pregnancy loss about in vitro fertilization with preimplantation genetic screening

Dr. Shahine and colleagues (1) highlight an important aspect of IVF-preimplantation genetic screening (PGS) that is often overlooked in counseling patients with diminished ovarian reserve (DOR) and recurrent miscarriage. In their article, ‘‘Higher rates of aneuploidy in blastocysts and higher risk of no embryo transfer in recurrent pregnancy loss patients with diminished ovarian reserve undergoing in vitro fertilization,’’ they demonstrate that many patients who undergo IVF-PGS do not reach ET owing to the culmination of low embryo number and high aneuploidy rate (1). The average age of the women in this study was 36.1 for normal responders and 37.0 for DOR patients (P1⁄4 .09). The live-birth rate per cycle with embryo biopsy was 47.5 % in the normal responding recurrent pregnancy loss (RPL) patients and 35% in the DOR-RPL patients; however, these statistics likely understate the effect of DOR on IVF-PGS outcomes as they exclude the eight DOR patients who did not make it to retrieval and the nine patients who either had no blastocysts to biopsy or opted out of PGS. The clinical miscarriage rates after euploid ET were 10% and 14%, respectively. The main finding of this paper is that the risk of not having a euploid blastocyst available for transfer in an IVF-PGS cycle was 13% in the normal reserve group and 25% in the DOR group. Because this number does not include the eight patients with DOR who did not even make it to retrieval, we calculate the risk of no transfer for DOR patients was at least 37%. Proponents of IVF-PGS often quote high success rates and low miscarriage rates per euploid transfer in goodprognosis patients with normal ovarian reserve. Few studies have examined outcomes in a population with limited ovarian reserve. When counseling patients about success rates with IVF-PGS, it is important to quote not only success rates per transfer but also the likelihood of having a euploid blastocyst available for transfer. An additional finding from this paper is that in women younger than 38, patients with DOR and RPL had higher aneuploidy rates than their age-matched RPL counterparts, leading to a worse than expected prognosis in this subset of RPL patients. Women over 38 years appeared to have similar aneuploidy rates in their embryos regardless of ovarian reserve testing. It is unclear but inferred from this data set that young women with DOR and RPL may have higher aneuploidy in their miscarriages. This could reflect that DOR in younger patients is more pathological, while DOR as defined by the authors in patients ages 38 and older may be physiological. If this is confirmed in additional studies, it may lead

Assisted Hatching: The Physiology of Blastocyst Hatching, the Use of Assisted Hatching in Assisted Reproduction, and a Survey of the Current Evidence Supporting its Use

The hatching of the developing blastocyst through the zona pellucida, the glycoprotein coat that facilitates fertilization and protects the embryo during early growth and transport through the reproductive tract, is critical for the direct embryo–endometrium interface needed for implantation. An abnormally thickened or rigid zona pellucida may be a cause for some patients’ reproductive failures, and assisted hatching—a micromanipulation technique that artificially breaks or weakens the zona—may improve clinical pregnancy rates for specific patient populations with particularly poor prognoses.