Human progesterone receptor polymorphisms and implantation failure during in vitro fertilization

Polymorphic variants of the human progesterone receptor gene have been described, but their potential influence on in vitro fertilization outcome have not been studied.

DNA was available from 317 women (cases) who had >or=2 embryo transfers without a clinical pregnancy and from 288 women (control subjects) who became pregnant after 1 in vitro fertilization attempt. With protocols that were specific for H770H (C/T genotype) and +331G/A polymorphism, amplification of polymorphism fragments, digestion with restriction enzymes, and gel visualization were performed.

Allele frequencies for the 2 variants were 15.5% for H770H T and 4.1% for +331A in cases and 17.9% and 3.6% in control subjects, respectively. Both polymorphisms were rare among non-white subjects. Possession of a H770H T allele was associated with a decreased risk for implantation failure, which was nonsignificant overall but significant in women aged <35 years (adjusted relative risk, 0.52 [95% CI, 0.28, 0.97]). Possession of a +331A allele was associated with an increased risk of implantation failure, which was nonsignificant overall but significant in women who weighed <135 pounds (adjusted relative risk, 3.85 [95% CI, 1.20, 12.30]). The +331G/A polymorphism tended to increase the risk for implantation failure in women with an H770H C/C genotype, but not in women with a C/T or TT genotype (P=.09). Among white women who were H770H C/C, there was a significant trend (P=.03) in the proportion of +331G/A carriers as the number of implantation failures increased, from 8.6% of women with 0 failed attempts to 40% among women with >or=5 failed attempts.

Although human progesterone receptor polymorphisms do not clearly affect the risk for implantation failure in most women who undergo in vitro fertilization, the likelihood that a woman carries the +331G/A human progesterone receptor polymorphism increases with the number of failed attempts at implantation.