The origin of biochemical pregnancies: lessons learned from preimplantation genetic diagnosis (PGD)

Abstract

Objective: Biochemical pregnancies (BP) are a relative frequent fenomenon observed in assisted reproduction (AR). The etiology of BP is not well understood, although either a problem of endometrial receptivity or an embryo of lower quality seem to be most plausible causes. Since there is a high incidence of aneuploidy in embryos derived from AR, many authors have proposed aneuploidy as the main cause of BP. The use of PGD has allowed the diagnosis of aneuploidy in preimplantation embryos. Although we are only able to analyze approximately 30% of the chromosomes present in a human embryo, it is accepted today that embryos screened for these chromosomes can be considered as normal embryos. Thus, the incidence of BP should decrease in a PGD program. Design: Retrospective study. Materials/Methods: We have retrospectively analyzed the pregnancies obtained in our PGD program (Group 1) during a two-years period. They were matched to two control groups of women undergoing IVF at the same time, having embryo replacement on days 6 (Group 2) or 3 (Group 3). BP was defined as a Beta hCG level >5 mIU/mL 14 days after ovum pick-up, the ultrasound scan resulting negative a week later after appropriate exclusion of ectopic pregnancies. All the regular IVF parameters were compared among groups. A total of 62 pregnancies were recorded after the analysis of chromosomes 13, 16, 18, 21, 22, X and Y in the embryos, and the same number of cycles were included in the controls. Results: All three groups displayed similar implantation rates per embryo replaced (51.3%, 47.3% and 50.2%, respectively). There was no difference among groups in the percentage of BP (25.8%, 25.8% and 24.2%, respectively). Significantly (p = 0.02) serum E2 levels were observed in Group 1 as compared to Group 3. Conclusions: These data suggest that aneuploidy is not the main cause of biochemical pregnancies in AR. Rather, an abnormal endometrial milieu probably due to aggressive stimulation of the ovaries seems to be the main cause, as ascertained by the transfer of chromosomally normal embryos in PGD. Supported by: IVI Valencia.