The purpose of this proposal is to outline suggested clinical pathways for the management of infertility and common reproductive endocrinology problems. The goal is to create an approach that provides the greatest success while using limited resources in the most cost-effective fashion.
A traditional approach to the management of Reproductive Endocrinology & Infertility problems can be found in any traditional text. However, most texts do not take into account the limited availability of resources within a managed care environment, and do not address the issue of stratification of care into that provided by an OB/GYN generalist and that provided by the reproductive endocrinology subspecialist. To that end, this outline will attempt to focus on what care is best provided by which practitioner. To design a cost-effective, medically appropriate evaluation and treatment plan, we must take the patient's age into consideration. While there is little necessity to initiate aggressive therapy for the 20 year old with unexplained infertility, those over 35 deserve a more aggressive approach.
Initial Infertility Evaluation Complete history and physical examination
Obtain all previous medical records for treatment related to infertility, hormonal or menstrual disturbances, anovulation, gynecologic surgery, or pelvic infection. Appropriate medical information should be gathered on the husband. Particular attention needs to be directed toward a review of medications that may interfere with fertility (i.e. Calcium channel blockers or atorvastation in males) or those that might be teratogenic.
Initial Medical Laboratory Evaluation
TSH, Prolactin, CF screen, CBC, ABO, RH-Type and antibody screen, HIV, HBsag, HCab, VDRL, Chlamydia/GC DNA probe, PAP smear, midluteal am progesterone above 10 ng/ml suggests normal ovulation. (Progesterone levels may drop up to 50% by the afternoon and after a meal.)
Evaluation of Ovulation
BBT charts from up to 3 months may be reviewed. While patients may be encouraged to initially record BBTs, these charts are only of value retrospectively determining that the patient has in fact ovulated and are of little value predicting when ovulation will occur.
Individualized Laboratory Testing
African American: Sickle screen and thalasmeia as appropriate.
Over 30 : FSH and estradiol may be obtained on cycle day 3 along with an antral follicle count ultr. Antimullerian Hormone, AMH testing can be done on any cycle day.
FSH values above 10 miu/ml or AMH <0.4 should result in REI review. Ultrasound screening for ovarian volume and antral follicle count on cycle day 3 may enhance the sensitivity of ovarian reserve monitoring
Irregular Menses : DHEAS should be obtained. Values above 250 ug/dl, although still in the normal range, may be seen in patients with polycystic ovary syndrome. These patients usually benefit from metformin therapy before ovulation induction with letrozole. For those above 600 ug/dl, consultation should be considered.
Irregular Menses with Hirsutism, Acne or Obesity: Many of these patients benefit from metformin combined metformin & pioglitazone Actoplusmet, or pioglitazone therapy whether or not they meet the diagnostic criteria for PCOS. A 2-hour insulin glucose tolerance test is likely to be the earliest test to indicate insulin resistance. A simple glucose tolerance test without insulin levels would not be adequate to predict who might benefit form therapy with an insulin lowering medication. Obese patients with markedly increased insulin levels may benefit from treatment with insulin injections with weight loss and improved lipid status.
The free testosterone panel may be helpful to monitor the effectiveness of metformin therapy. Fasting am 17 hydroxyprogesterone is ordered during the follicular phase if adult onset congenital adrenal hyperplasia is suspected. Values above 150 deserve referral for cortrysyn stimulation testing. If the patient appears Cushingoid, decadron 1mg is administered at midnight and an 8am fasting cortisol level is obtained the next morning. If PCOS is suspected, cardio C-reactive protein, homocysteine and a lipid panel should be ordered.
Low risk for tubal disease: For patients without a history of pelvic pain, surgery, dysmenorrhea or dyspareunia, a serum chlamydia IgG antibody panel should be obtained. As tubal disease or peritubal adhesions are the frequent sequalae of asymptomatic chlamydia infection, more aggressive evaluation of the fallopian tubes and pelvis are required if an elevation is noted. Alternatively, IVF may be a more cost effective approach if the risk of significant tubal disease is high.
Semen Analysis: Testing should be obtained before any invasive procedure such as HSG, laparoscopy, or ovulation induction is considered. A semen analysis is considered current if it has been obtained within the last 12-18 months. If the male has had a recent febrile illness, testing should be postponed 2-3 months. Abnormal values should be rechecked no sooner than 4-8 weeks. If on repeat, the total motile count per sample is greater than 5 million, ovulation induction and intrauterine insemination may be of benefit. Varicocele repair is controversial and should only be considered if the varicocele is rather large. If WBC's are present, prolonged antibiotic therapy may be considered. A serum prolactin, FSH, testosterone and sperm antibody testing should follow abnormal semen analysis. A Sperm Chromatin Structure Assay (SCSA) measures sperm DNA fragmentation and identifies men with low fertility potential. An SCSA test may be considered for men with a history of varicocele, cryptorchid testes, chemotherapy, testicular cancer, radiation exposure, pesticide exposure, long distance bike riding or unexplained infertility.
For those with azoospermia, FSH, free testosterone panel, estradiol, chromosomal analysis and Y microdeletion tests are indicated.
Tubal Factor Infertility
- Assessment of Risk Factors:
- Dysmenorrhea, if associated with pelvic tenderness, uterosacral nodularity or perimenstrual diarrhea, should be considered evidence of endometriosis.
- Previous pelvic surgery
- IUD complications such as removal for pain, bleeding or infection
- History of PID<
- Elevated chlamydia IgG titers
Evaluation of Tubal Factors
- Over 35, > 3 years infertility & risk factors: Tubal patency should be determined preoperatively to rule-out proximal tubal obstruction that can be treated during an initial laparoscopic procedure. Laparoscopy or IVF should be considered early in the evaluation.
- Low risk factors, anovulatory infertility or AID candidates: HSG may be delayed if no risk factors are present. Ovulation induction or AID (donor insemination) may be considered for 3-4 cycles before considering HSG. A recent study has shown that one additional pregnancy will occur for every 60 diagnostic laparoscopies performed in women with low risk of tubal disease resulting in a cost of~$600,000 per additional pregnancy. IVF is far more cost effective than diagnostic laparoscopy in women without significant risk factors.
Post-coital Testing has not been shown to correlate well with fertility and therefore is rarely indicated.
Endometrial Biopsy: The routine use of endometrial biopsy to confirm the adequacy of luteal phase has poor predictive value for the management of infertility. It is only indicated for those patients with regular cycles and recurrent pregnancy loss. Endometrial biopsy, therefore, is not indicated in the diagnosis of infertility.
Initial Treatment for InfertilityEmpirical Treatment
Female patients are treated with prenatal vitamins. Both male and female partners may be empirically treated with suitable antibiotics for presumed ureaplasma infection. Prevalence of this infection is > 35% and treatment costs roughly one-tenth the cost of culture evaluation. Males are started
The risks of genetic abnormalities are discussed for those with a family history or age > 35. Smoking cessation, alcohol reduction, weight loss and marital counseling are recommended as indicated. Males are encouraged to avoid hot tubs, saunas, steam baths and hot baths.