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The vast majority of embryos produced in vitro and transferred fail to develop into an infant, supporting the concept that only a small fraction of embryos is destined to become a live birth. One of the main reasons for such a low embryo-to-infant ratio is the remarkably high number of embryos that after preimplantation genetic diagnosis are found to have a chromosome imbalance. This study reports the overall biological wastage from oocytes inseminated to ongoing pregnancies in patients undergoing preimplantation genetic screening (PGS) because of advanced age, recurrent pregnancy losses or multiple failed IVF cycles. The analysis of biological wastage per oocyte showed that in this cohort of patients, of 333 eggs inseminated, 183 (55.0%) provided embryos for biopsy, and of these, only 33 (18.0% per embryo and 9.9% per oocyte) were normal. A total of 26 embryos were suitable for transfer (14% per embryo and 7.8% per oocyte), but only five (1.5%) implanted and three (1.0%) resulted in live births. In conclusion, there is enormous biological wastage during assisted reproduction, and the data obtained from both embryos and oocytes of patients undergoing PGS support the concept that many embryos and eggs obtained during IVF are intrinsically abnormal and thus fail to implant.

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Our findings strongly indicate FSHR variants as being an intrinsic genetic cause of some forms of infertility and identify a need for functional characterization of these variants and the investigation of more individualized ovarian stimulation protocols.