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Background: Luteal phase deficiency (LPD) was recognized as a potential cause of infertility well before the first attempts at ovarian stimulation and in vitro fertilization (IVF). However, in the subsequent IVF era, the fact that LPD is particularly frequent in the context of ovarian stimulation has driven the attention to LPD almost exclusively to stimulated cycles. Here we re-assess the role of LPD as the primary cause of infertility and suggest a possible solution. Patients and Methods: This study involves 12 young couples with unexplained infertility who attended our clinic for an assisted reproduction attempt. All of the female partners had low serum progesterone concentrations on day 21 of their menstrual cycle, in spite of the presence on an apparently functional corpus luteum. The female patients underwent repeated ultrasound scans during three subsequent cycles to determine the day of spontaneous ovulation. They were counselled to have frequent sexual intercourse when the dominant follicle reached the size of >17 mm, and progesterone was administered daily, by vaginal route, in all of them beginning with the day on which ovulation had been confirmed. Results: Out of the 12 women included in this study, six became pregnant naturally during one of the three progesterone-supplemented cycles. Progesterone supplementation was discontinued progressively, based on repeated serum progesterone determinations during the early pregnancy. All of the pregnancies were singleton. One of them ended in a miscarriage, while the others went to term, resulting in the birth of five normal children. Conclusions: Our data suggest that LPD during natural ovulatory cycles may be more frequent than believed. In the present study, no other apparent causes of infertility were detected. In such cases, assisted reproduction techniques can be avoided and replaced by individualized progesterone supplementation during the early luteal phase.

The Neglected Luteal Phase after Natural Conception: Rescue by Early Progesterone Supplementation