Unexplained Infertility and Folliculo-Luteal Function

  • György Siklósi


Hormonal stimulation therapies increase spontaneous pregnancy rates by several times (from 1–3 % up to 10–15 %) in unexplained infertility (UI) (normospermia, intact female anatomical features, verified ovulation). In light of this, we presumed that the cause of UI is the hormonal insufficiency of ovulatory cycles: low preovulatory oestradiol (E2), based on which insufficient luteal P and E2 levels can lead to the formation of a deficient secretory endometrium, which is inappropriate for implantation and placentation (folliculo-luteal insufficiency, FLI). The luteal P level is significantly (p < 0.001) lower in UI than the physiological value (11.3 ± 3.3 and 29.2 ± 3.1 ng/ml).

In 658 UI patients (aged between 20 and 45 years, 30.3 years on average; 2–17-year infertility period, 4.4 years on average), we normalised folliculo-luteal function (FLF) (P > 23 ng/ml) using clomiphene citrate and/or dexamethasone treatment and investigated its effect on the patients’ fertility.

The monthly pregnancy rate (MPR) was an average of 28.9 % during the first three cycles, and the 12-month average was 26.6 %.

The cumulative pregnancy rate (CPR) was 64.1 %, 82.5 %, 90.3 % and 93.5 % over 3, 6, 9 and 12 months, respectively. In patients who continued treatment for 12 months (N = 625), the 12-month CPR was 98.4 % during the first treatments.

Time to pregnancy (TTP) with physiological FLF was 3.14 ± 2.4 cycles during the first treatments (N = 625).

In the untreated control group (N = 147, age of 20–45 years, average of 30.3 years; infertility period of 2–14 years, average of 4.2 years), 102 pregnancies occurred in 72 patients (49 %) over 8 years. CPR over 6 and 12 months were 8.8 and 13.6 % in this group.

According to our results, the main cause of UI is folliculo-luteal insufficiency, which remains unrecognised by the currently used diagnostic methods: the normalisation of FLF – based on the diagnostic parameters we developed – resulted in physiological fertility.


Pregnancy Rate Preterm Birth Pregnancy Outcome Clomiphene Citrate Untreated Control Group 
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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • György Siklósi
    • 1
  1. 1.Semmelweis University Second Department of Obstetrics and GynecologyBudapestHungary

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