Belinda M. Sartor

Effect of diagnosis, age, sperm quality, and number of preovulatory follicles on the outcome of multiple cycles of clomiphene citrate-intrauterine insemination

OBJECTIVE To determine how diagnosis, age, sperm quality, and number of preovulatory follicles affect pregnancy rates when multiple cycles of clomiphene citrate (CC)-IUI are performed. DESIGN Fifteen-year prospective observational study. SETTING Private infertility clinic. PATIENT(S) Three thousand, three hundred eighty-one cycles of husband or donor IUI. INTERVENTION(S) Ovulation induction with CC and IUI. MAIN OUTCOME MEASURE(S) Per-cycle pregnancy rate (PR), cumulative pregnancy rate (CPR). RESULT(S) Pregnancy rates remained constant through four cycles, then fell significantly for diagnoses other than ovulatory dysfunction. Mean PRs for cycles 1-4 were significantly lower for patients with the following characteristics: age >/=43 years, poor semen quality, single preovulatory follicles, and diagnoses other than ovulatory dysfunction. Additional cycles of CC-IUI compensated for low PRs because of age, semen quality, or number of follicles. After four cycles, CPRs were 46% for ovulatory dysfunction; 38% for cervical factor, male factor, and unexplained infertility; 34% for endometriosis; and 26% for tubal factor. After six cycles, CPRs were 65% for ovulation dysfunction, 35% for endometriosis, and unchanged for other diagnoses. CONCLUSION(S) Clomiphene citrate-intrauterine insemination should be performed for a minimum of four cycles. Additional cycles of CC-IUI can compensate for low pregnancy rates due to age, semen quality, or follicle number in patients with ovulation dysfunction.

Relationship of follicle numbers and estradiol levels to multiple implantation in 3,608 intrauterine insemination cycles

OBJECTIVE To determine the relationship of follicle numbers and estradiol (E(2)) levels to multiple implantations in human menopausal gonadotropin (hMG) and clomiphene citrate (CC) cycles. DESIGN Fifteen-year prospective study. SETTING Private infertility clinic. PATIENT(S) Women who underwent 3608 cycles of husband or donor intrauterine insemination (IUI). INTERVENTION(S) Ovulation induction (OI) with CC, hMG, or CC+hMG. MAIN OUTCOME MEASURE(S) Pregnancy and multiple implantations. RESULT(S) Triplet and higher-order implantations-but not twin implantations-were related to age, E(2) levels, and number of follicles > or = 12 mm and > or = 15 mm, but not number of follicles > or = 18 mm, in hMG and CC+hMG cycles. For patients less than 35 years old, three or more implantations tripled when six or more follicles were > or = 12 mm, in CC, hMG, and CC+hMG cycles, and when E(2) was > or = 1000 pg mL in hMG and CC+hMG cycles. For patients 35 or older, pregnancy rates in hMG and CC+hMG cycles doubled when six or more follicles were > or = 12 mm, or E(2) levels were >1000 pg mL, whereas 3 or more implantations were not significantly increased. CONCLUSIONS Withholding hCG or IUI in CC, hMG, and CC+hMG cycles when six or more follicles are > or = 12 mm may reduce triplet and higher-order implantations by 67% without significantly reducing pregnancy rates for patients under 35 years of age.

Polycystic ovarian syndrome and the metabolic syndrome.

Polycystic ovarian syndrome (PCOS), first described in 1937, was defined by specific ovarian histopathology and a constellation of signs and symptoms. Through the years, the etiology remained elusive, with heated debates focusing in turn on the ovary and then the pituitary as the causative agents. In the last several decades, it has become clear that insulin resistance makes up a very important component of this syndrome. With this knowledge, new therapies have emerged along with the realization that PCOS and the metabolic syndrome are closely related through their shared insulin resistance. In this review, the diagnosis, pathophysiology, and therapy of PCOS are discussed and upon this background, those areas held in common by PCOS and the metabolic syndrome are explored.

Infertility is a symptom, not a disease

Just as the symptoms chronic headache, chronic stomach pain, and chronic chest pain may be caused by underlying disease, so may infertility be caused by underlying disease. Endometriosis, uterine fibroids, benign ovarian tumors, and pelvic adhesive disease are causes of infertility that can be treated by laparoscopy, if detected early, but may require more extensive surgery later if they remain undiagnosed. Anovulation may be due to insulin resistance that can result in diabetes or cardiovascular disease later in life (2) or any of a number of other endocrine disorders with lifelong effects. A 1991 study from the Centers for Disease Control and prevention (CDC) found that the lifetime risk of developing endometrial cancer was increased not only in patients with polycystic ovary syndrome but also in infertile patients with hypothyroidism, uterine fibroids, and endometriosis (3). Infertile women with any of these conditions who conceived a term pregnancy did not have an increased risk of endometrial cancer. A major obstacle to the treatment of infertility as a symptom by the Health Insurance Industry is the way it is characterized in the International Classification of Diseases, Volume 9 (ICD). In the ICD, female infertility (Code 628.0) and male infertility (606.0) are classified as diseases but are clearly treated as symptoms. Female infertility is listed as “associated with,” “due to,” or “having its origin in” 30 other conditions. Similarly, male infertility is listed as “due to” 12 other conditions. Anovulation is given the same diagnostic code number as female infertility (628.0) and is not classified further as to its underlying causes. Health insurers have taken advantage of this to deny coverage for endocrine evaluation of patients with anovulation on the basis that it is synonymous with infertility.