Lessons from elective in vitro fertilization (IVF) in, principally, non-infertile women.
BACKGROUND
We here report the first investigation of exclusively elective in vitro fertilization (IVF) cycles in women with no apparent history of infertility. Since IVF outcome in women with infertility are always influenced by underlying causes of infertility, a study on non-infertile women may offer new insights.


METHODS
We investigated 88 females without history of infertility in 109 consecutive elective IVF cycles, almost exclusively performed for purposes of preimplantation genetic screening (PGS; i.e., elective gender selection). The following questions were addressed: (i) impact of PGS on IVF pregnancy chances; (ii) impact of transfer of 1 vs. ≥2 embryos on IVF pregnancy chances; (iii) correlation of anti-Müllerian hormone (AMH) levels to embryo ploidy (iv) effect of gonadotropin dosage used in stimulation on available embryos for transfer; and (v) in form of a 1:1 case control study, compared 33 elective PGS cycles with matched control cycles without PGS, performed in couples with either prior tubal ligations and/or severe male factor infertility as indication of IVF.


RESULTS
The overall clinical pregnancy rate for the group was 36.7%; pregnancy was associated with number of euploid (P = 0.009) and number of embryos transferred (P = 0.001). Odds of pregnancy were 3.4-times higher if ≥4 euploid embryos were produced in comparison to <4 (95% CI 1.2 to 9.2; P = 0.019), and odds of pregnancy were 6.6-times higher if greater than or equal to 2 rather than <1 euploid embryos were transferred (95% CI 2.0 to 21.7; P = 0.002). Increasing AMH (P = 0.001) and gonadotropin dosage used in ovarian stimulation (P = 0.024), was, independently, associated with number of available euploid embryos. Increasing AMH, but not follicle stimulating hormone (FSH), was associated with number of embryos available for biopsy and PGS (P = 0.0001). Implantation rates were 26.4% with PGS and 9.5% without (P = 0.008). Women undergoing PGS, demonstrated 4.58-times higher odds of pregnancy than matched controls (95% CI 1.102 to 19.060, Exp 4.584, P = 0.036).


CONCLUSIONS
This study suggests that outcomes of elective IVF cycles may significantly deviate from infertility-associated cycles. Affirming proof of concept for PGS, utilizing day-3 embryo biopsy and fluorescence in-situ hybridization (FISH), both widely held responsible for earlier failures to establish such proof, suggests that the principal cause of prior failures were likely not insufficient laboratory techniques but poor patient selection for PGS. Such a conclusion questions the current reintroduction of PGS with improved techniques and technologies in absence of prior determination of suited patient populations.
Center for Human Reproduction, New York, NY 10021, USA. ngleicher@thechr.com
Norbert
N
Gleicher
Ann
A
Kim
Andrea
A
Weghofer
David H
DH
Barad
D000328:Adult; D054304:Anti-Mullerian Hormone / Q000097:blood; D004624:Embryo Transfer / Q000379:methods; D004622:Embryo, Mammalian; D005260:Female; D005307:Fertilization in Vitro; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage; D006801:Humans; D007246:Infertility; D007247:Infertility, Female; D008297:Male; D008596:Menotropins / Q000008:administration & dosage; D011003:Ploidies; D011247:Pregnancy; D018873:Pregnancy Rate; D019836:Preimplantation Diagnosis / Q000379:methods; D012743:Sex Preselection; D056826:Single Embryo Transfer; D016896:Treatment Outcome
D008596:Menotropins; D054304:Anti-Mullerian Hormone; D005640:Follicle Stimulating Hormone