Interpretation:
There are strong scientific evidences in the literature suggesting there may be a relationship between the uterine cavity abnormalities and PCOS disease which comprised with abnormal sex steroid and AMH levels in utero and adult life. It has been known that correct patterning and differentiation of the Müllerian Duct is dependent on a complex network of Hox and Wnt genes.5-14 And these genes are regulated mainly AMH and sex steroids which both of them are main topics of PCOS under discussion. It has been shown that the patients with HOXA10 mutations had uterine defects ranging from septate uterus to a didelphys uterus indicative of MD fusion defects.15,16 In a review, it was clearly shown that intrauterine hyper-exposure to testosterone influences the expressing genes.17 There may be other mechanisms be responsible for increased intrauterine hyper androgens linked with intrauterine AMH function. During normal pregnancy, the fetus is protected from maternal androgens by placental aromatase. It is possible, however, that placental dysfunction may expose the fetus to higher concentrations of androgens, although it has yet to be proven empirically but shown that Anti-müllerian hormone was able to reduce placental aromatase activity.18,19 Also, recent evidence has shown that GnRH-positive neurons express AMH receptors and that exogenous AMH potently increases GnRH neuron firing and GnRH release in murine living tissue explants.20 Prenatal AMH treatment triggers the neuroendocrine disturbances of PCOS in the offspring via GnRH neuronal activation.21
Also, the high levels of maternal serum AMH levels during pregnancy in PCOS patients may be a cause of formation of PCOS in female fetus in utero. Since AMH is secreted from granulosa cells in females, AMH secretion is not expected until the granulosa cells activated. Previous studies reported that the expression of AMH in the ovary is switched on soon after birth and concluded that there is no detectable ovarian production during normal fetal.22-24 Although this, many authors reported that the expression patterns of AMH within human fetal ovarian specimens, in the end of gestation at 36 weeks in granulosa cells of preantral follicles.25-27 The different structure and physiology of granulosa cells in PCOS patients may also be in the intrauterine period and cord blood AMH levels may be higher in the in female fetuses, whom will later develop PCOS. Tata B et. all reported that AMH levels is higher in pregnant PCOS subjects than in pregnant control women and suggested that elevated prenatal anti-mullerian hormone reprograms the fetus and induces polycystic ovary.21 However, umbilical cord blood AMH and sex steroid levels of later developing PCOS patients in intrauterine period is not known.
The estimated prevalence of müllerian abnormalities is approximately 5 %, from mild to severe, in the general population and increase up to 13 % in women with infertility.27 We were not able to find an article published among the frequency of uterine abnormalities in PCOS patients in the literature. Our research is the first research seeking up the relationship between the shape of uterine cavity and PCOS.
In our study, the frequency of the abnormal uterine cavity was statistically significantly higher in PCOS group than controls when evaluated in both classifications. According to the both classifications, The frequency of U1a, U2a, U2b (ESHRE-ESGE) and Va, Vb,VII (ASRM) was found statistically significantly higher in PCOS group than controls as subgroup analysis.
The frequency of type VI cavity (arcuate) considered as an abnormality to ASRM but as a variation of normal to ESHRE-ESGE was not different in PCOS and control patients which support the assertion of ESHRE-ESGE.
The hypothesis and mechanisms reported in the literature to explain the possible relationship between uterine abnormalities and PCOS were shown in Figure-3. In sight of these hypothesis, it would be expected to find the serum AMH levels much higher in the patients who had uterine abnormality but we could not find any differences and correlation between the levels of AMH and uterine abnormality. We think that this may be related not to maternal AMH levels but related to umbilical cord AMH levels. The only study in the literature focusing thoroughly this topic by Hart R et all., maternal blood samples were collected at 18 and 34 weeks and umbilical cord blood was collected at 870 singleton deliveries. The cohort included 1800 adolescents aged 16 to 18 years. Cord blood of adolescent girl was available for 77 of the 244 girls consented to research. No statistically significant associations between maternal and cord androgens and AMH in adolescents were found.28
Positive correlation was found between the frequency of uterine cavity abnormality and maternal serum free testosterone levels according to ESHRE-ESGE classification. The explanation of lack of correlation when ASRM classification was taken into consideration is that the arcuate uterine cavity is accepted as normal in ESHRE-ESGE classification.
Positive correlation between serum free testosterone levels and the presence of intrauterine cavity abnormalities can be explained that the resorption process may not be completed intrauterine period and may be under process during adulthood.
PCOS is associated with a variety of complications in pregnancy, including risk of miscarriage and preterm birth.2-4The pathophysiological mechanisms behind the increased risk of adverse pregnancy outcomes among women with polycystic ovary syndrome are not fully known. This association may be explained with the presence of uterine abnormalities. The question looking forward to be answered is the relationship between increased pregnancy complications and uterine cavity abnormalities.