Polycystic ovary syndrome, infertility, familial thrombophilia, familial hypofibrinolysis, recurrent loss of in vitro fertilized embryos, and miscarriage.
OBJECTIVE
To study reversible determinants of infertility and recurrent loss of transferred embryos after failure of 7 of 10 embryo transfers, 1 live birth, and 2 miscarriages.


METHODS
Measures of thrombophilia, hypofibrinolysis, reproductive hormones, and androgenic steroids before and after metformin therapy.


METHODS
Outpatient clinical research center.


METHODS
A 32-year-old amenorrheic, infertile woman with polycystic ovary syndrome (PCOS) who had 7 of 10 embryo transfers fail, 1 premature live birth, and 2 miscarriages at 8 and 17 weeks.


METHODS
Metformin (2.55 g/d) was given to ameliorate the endocrinopathy of PCOS.


METHODS
Coagulation, insulin, reproductive hormones, and androgenic steroids.


RESULTS
The propositus had thrombophilia (familial protein S deficiency [free protein S 32%; normal >/=65%]). She also had familial hypofibrinolysis with 4G4G polymorphism of the plasminogen activator inhibitor (PAI-1) gene and high PAI-1 activity (PAI-Fx), 42.5 U/mL, normal <21.1. Polycystic ovary syndrome was characterized by amenorrhea, polycystic ovaries, high fasting serum insulin (39 microU/mL, normal <20), androstenedione (763 ng/dL, normal <250), and testosterone (229 ng/dL, normal <83). After she received metformin for 4 months, PAI-Fx normalized (12.4 U/mL), as did insulin (12 microU/mL), androstenedione (185 ng/dL), and testosterone (39 ng/dL); weight fell from 109 to 91.3 kg (16%).


CONCLUSIONS
Metformin reversed the endocrinopathy of PCOS. Familial thrombophilia and hypofibrinolysis may lead to thrombosis-mediated uteroplacental vascular insufficiency, failure to achieve pregnancy after embryo transfer, and miscarriage.
Glueck
C J
CJ
Cholesterol Center, Jewish Hospital, Cincinnati, Ohio 45299, USA. glueckch@healthall.com
Awadalla
S G
SG
Phillips
H
H
Cameron
D
D
Wang
P
P
Fontaine
R N
RN
D000026:Abortion, Habitual; D000328:Adult; D000568:Amenorrhea / Q000150:complications; D000735:Androstenedione / Q000097:blood; D004624:Embryo Transfer; D005260:Female; D005307:Fertilization in Vitro; D005342:Fibrinolysis / Q000235:genetics; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007247:Infertility, Female / Q000150:complications / Q000378:metabolism* / Q000628:therapy*; D008687:Metformin / Q000627:therapeutic use; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics; D011085:Polycystic Ovary Syndrome / Q000150:complications* / Q000628:therapy; D011110:Polymorphism, Genetic; D011247:Pregnancy; D013739:Testosterone / Q000097:blood; D019851:Thrombophilia / Q000150:complications* / Q000235:genetics; D016896:Treatment Outcome
D007004:Hypoglycemic Agents; D017395:Plasminogen Activator Inhibitor 1; D013739:Testosterone; D000735:Androstenedione; D008687:Metformin