A 32 years old man and his 28 years old wife are married for the past 4 years and are anxious to conceive. There is history of three previous early pregnancy losses. The wife has history of Polycystic Ovarian Syndrome for which she is on Metformin.

1.  The possible etiological causes for the recurrent pregnancy loss are all except

(a) Insulin resistance

(b) Impaired progesterone production

(c) Leiomyoma of the uterus

(d) Imbalance between levels of LH and FSH

Answer: The answer is (c). This woman has Poly Cystic Ovarian Syndrome (PCOS). Therefore there is a risk of insulin resistance. This has been shown to cause increased pregnancy loss. PCOS is also associated with impaired progesterone production and action. PCOS is characterized by imbalance between LH and FSH both of which are required for progesterone and estrogen secretion and for ovulation. Though leiomyoma of the uterus can be a cause for the pregnancy loss, in this patient with a history of PCOS the other choices are more suitable.

2. The mechanism of pregnancy losses in Poly Cystic Ovarian Syndrome includes all the following except:

(a) Delayed ovulation giving rise to non-viable ova

(b) Impaired progesterone synthesis and action

(c) Excess of IL-1 and TNF alpha in the endometrium

(d) Insulin resistance.

Answer: The answer is (c). Insulin resistance is one of the proposed mechanisms of recurrent pregnancy loss in PCOS. Delayed ovulation and impaired progesterone actions are mechanisms which have been substantiated with in vitro studies. Cytokins and prostaglandins play an important role in sustaining a pregnancy, but excess IL1 and TNF alpha is not the mechanism of pregnancy loss in PCOS.

3. The woman got pregnant for the fourth time while on metformin. At this point the most appropriate action would be to

(a) Stop the metformin, as oral hypoglycemics are contraindicated in early pregnancy

(b) Switch over to Insulin.

(c) Continue metformin as it has been shown to protect from pregnancy loss

(d) Switch to Sulphonylureas.

Answer: The answer is (c). A retrospective study of all PCOS women seen in an academic endocrinology clinic within the past 4.5 yr and who became pregnant during that time were studied. 65 women got Metformin and 31 did not. The early pregnancy loss rate with Metformin was 8.8% (6 of 68 pregnancies), compared with 41.9% (13 of 31 pregnancies) for non Metformin takers. In each group of women, those who had a prior history of miscarriage, the loss rate was 11.1% (4 of 36 pregnancies) for those taking Metformin, 58.3% (7 of 12 pregnancies) without. Metformin administration during pregnancy reduces first-trimester pregnancy loss in women with the polycystic ovary syndrome.