Does Low Stimulation Make Eggs Better?

Low stim does not “make eggs better”.  If it did, everyone would use such a protocol for all patients; the idea is to use the lowest effective dose to get the ovarian response you are looking for.  These medications do not make eggs better or worse genetically or developmentally. 

Click here to view more information on the study.

The odds of embryonic aneuploidy in patients with a normal ovarian response is not influenced by the cumulative dose of gonadotropins used for controlled ovarian stimulation.

In this particular study, the association between gonadotropin exposure and aneuploidy was assessed.

Controlled ovarian hyperstimulation (COH) promotes multifollicular growth, broadening the chance of securing euploid embryos that will successfully implant. Whether aneuploidy is increased from COH with exogenous gonadotropins interfering with the natural selection of dominant follicles is a concern.

Kruskal-Wallis tests and logistic regression with generalized estimating equations (GEEs) were used for data analysis.  Polymerase chain reaction (PCR) was used to assess aneuploidy. This is a retrospective cohort study of 828 patients that underwent 1122 IVF cycles involving controlled ovarian stimulation and trophectoderm biopsy for preimplantation genetic screening (PGS), from 2010 to 2015.

Broadly, there was no significant association between cumulative gonadotropin (GND) dose and the odds of aneuploidy after controlling for patient age, ovarian reserve, stimulation protocol, days of stimulation, and diagnoses. Equivalently, in cycles where patients did not require COH beyond cycle day 12, there was no compelling association between cumulative gonadotropin dose and the odds of aneuploidy. Although, in cases where patients were stimulated past cycle day 12, there was a significant increase in the probability of aneuploidy with augmenting cumulative gonadotropin dose, with a small effect size. In this cohort, there was a 16.4% gain in the odds of aneuploidy for each 1000-u increase in cumulative GND exposure. When the analysis was restricted to low responders (peak estradiol <500 pg/mL or <4 mature follicles achieved; there was no significant association between gonadotropin dose and aneuploidy (adjusted OR = 1.12, 95% CI 0.982-1.28, p = 0.09), regardless of the duration of COH required to reach vaginal oocyte retrieval.

The degree of exposure to exogenous gonadotropins did not greatly modify the likelihood of aneuploidy in patients with a normal ovarian response to stimulation.  Patients requiring prolonged COH were demonstrated to have elevated odds of aneuploidy with increasing cumulative gonadotropin dose. This finding may reflect an increased tendency towards oocyte and embryonic aneuploidy in patients with a diminished response to gonadotropin stimulation.

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