by: Kevin J. Lederer, MD-Fertility Centers of Illinois
Ovulatory disorders are one of the most common causes of Infertility. About 25% of patients presenting with infertility will be determined to have an ovulatory disorder as the underlying cause. The history yields the most information regarding whether a woman is ovulating.
Folklore during training suggested that is not possible to determine if a woman is ovulating based on the history. Many anovulatory women will have breakthrough bleeding. However it is highly improbable that breakthrough bleeding will occur in a perfectly cyclic manner, mimicking normal menses. A woman with infrequent menses more than 35 days has a clear ovulatory disorder. If there is any doubt regarding Ovulation, premenstrual symptoms prior to her period also are strongly associated with prior ovulation in that Cycle. Sudden bleeding without premenstrual symptoms is more closely associated with non-ovulatory cycles. Urine LH Surge testing can be helpful but there are clear diurnal variation in LH levels. Many kits suggest that women test the first morning urine. This may not be accurate given that the LH surge usually occurs just prior to waking. It takes time for LH to be secreted in the urine. Testing around 12 PM may yield better results in those women reporting the absence of a color change. Cycles longer than 35 days translate into fewer ovulatory cycles when extended over a 1 year period. Given wide cycle variation it is difficult for couples to time intercourse. Many such patients have cycles every 35-90 days.
When evaluating a woman with an ovulatory disorder it is important to consider body habitus. A very thin body with low body fat around 20% or less can be found in elite athletes and patients with anorexia nervosa. These patients have functional hypothalamic amenorrhea. High BMI's also are related to ovulatory disorders. There is also the well known association with PCOS. The diagnosis of PCOS is dependent on the presence of 2/3 findings. Those findings are:
1. Irregular menstrual cycles, 2. PCOS ovaries at Ultrasound , 3.Clinical or laboratory evidence of hyperandrogenism. A woman with a high BMI should be encouraged to pursue a diet and exercise program. Even a 5-10% weight loss can lead to improvements in ovulation and may avoid the need for medication induced Ovulation Induction. Such patients should be encouraged to walk for 1 hour at least 4 days per week. Evidence suggests that given the relative insulin insensitivity associated with increasing BMI, a low carbohydrate, high protein (e.g. Atkins) theoretically should improve intraovarian androgen hyper secretion. It has also been suggested that such a diet may result in a greater and longer lasting weight loss. Patients with morbid obesity have vastly lower success rates with all fertility treatments. Given the low success rates of lifestyle changes in these women, they should be encouraged to investigate gastric surgery options.
All patients with an ovulatory disorder should have their thyroid and Prolactin; levels checked. Low or undetected FSH and LH levels suggest hypogonadotropic hypogonadism. Such patients are vastly less likely to ovulate on clomiphene and may require injectable gonadotropins. Given the neonatal risks of a Classic 21 Hydroxylase Deficiency, a fasting 17-OH Progesterone should be considered to rule out a partial 21 OH deficiency. Although found across many populations, it is more prevalent in woman of Ashkenazi Jewish and Hispanic heritage. A follicular phase 17-OH progesterone level above 100ng/dl should be followed-up with an ACTH Progesterone test to rule out a partial 21-OH deficiency. A DHEAS level should be checked to rule out a partial 11-OH deficiency. Such patients with a DHEAS above 300ng/d. benefit from the addition of glucocorticoids to their ovulation induction.
The proper evaluation of patients with PCOS is controversial. Patients with PCOS can have elevated androstenedione, total Testosterone, free testosterone, fasting hyperinsulinemia, fasting hyperglycemia or low sex- binding globulin levels. Single static levels may not be reflective of androgen Hormone physiology since there is significant diurnal and cycle variation in these levels. A formal GTT may be considered. A patient with a testosterone level more than 2 times above the assay maximum (especially with frank virilization) should be investigated for a testosterone producing tumor. Patients with truncal obesity, violaceous striae, buffalo hump or proximal muscle weakness should be screened for Cushing's syndrome with a 24 urine cortisol level.
For women attempting conception, ovulation induction should be initiated. If the diagnosis is PCOS, these women may benefit from addition of glucophage to their ovulation induction regimen. Glucophage should be started at a dose 500mg qd for the first week and titrated up to 1500-2000 mg in 3 divided doses per day. It should only be taken with meals. Recent studies have suggested that glucophage alone is not sufficient for reliable ovulation. PCOS patients need to have Clomid added to their ovulation induction treatment. For PCOS patients and those with nonspecific ovulatory disorders are treated with Clomid 50-150 mg x 5 days starting on cycle day 2-6. Any day between day 2-6 yields equivalent pregnancy success rates. The dose can be titrated to the patients cycle length. If a patient does not have a spontaneous menses within 4 weeks of her last Clomid or needs Provera, the dose should be increased. In patients resistant to Clomid, the dose can be increased to 100mg for 7 days. Finally the addition of 1mg of dexamethasone daily can induce ovulation in Clomid resistant patients. Patients over age 34 or those who fail treatment after 4 months should be considered for referral.
The care of women with an ovulatory disorder can be gratifying in that many respond to simple ovulation induction, This further strengthens their relationship with the physician who already coordinates their care. Instituting a simple evaluation and following a treatment algorithim can often yield an early treatment success.
We hope that you have found this to be an informative discussion. If we can be of further help to you or your staff regarding this, or any topic in our series of informational letters, please feel free to contact me or any of the physicians of Fertility Centers of Illinois directly, we are happy to speak with you.