Clomiphene citrate is preferred
Ovarian dysfunction can be treated with clomiphene for 3 to 6 cycles5 starting at 50 mg per day from cycle day 5 to 9 and increasing to 100 and then 150 mg per day if ovulation does not occur. The drug may also be effective empiric treatment for unexplained infertility using 100 mg per day from cycle days 3 through 7 for a maximum of 3 to 4 cycles.
Only gynecologists experienced with ovarian stimulation drugs and with access to daily ultrasonographic monitoring and estradiol levels should use them, because of the risk of multiple pregnancy and ovarian hyperstimulation.
For women with polycystic ovary syndrome (PCOS), clomiphene alone is more effective than metformin alone. Ovarian drilling may be an effective surgical treatment for PCOS if clomiphene fails, but the cost and risk of adhesions must be considered.
Human chorionic gonadotropin (hCG) injections during clomiphene treatment to stimulate ovulation should be given only if the patient’s own urinary LH surge cannot be detected.
A single intrauterine insemination (IUI) improves the pregnancy rate slightly in conjunction with clomiphene, and by an odds ratio of approximately 2 in conjunction with gonadotropins. The gonadotropin dosage ranges from about 75 to 600 IU per day for 8 to 12 days, based on patient need and careful monitoring.
When to give up on ovarian stimulation. Failure to achieve pregnancy after 3 to 6 cycles signals the need to expand diagnostic evaluation or change treatment strategies.
Evaluate the uterus and tubes
Uterine factors rarely cause infertility but warrant thorough investigation all the same, including assessment of uterine cavity size and shape. A number of methods are available:
- hysterosalpingography (HSG)
- ultrasonography
- saline sonohysterography
Peritoneal factors such as endometriosis or pelvic or adnexal adhesions may occasionally be identified by ultrasonography if there is a mass, but are more likely to require laparoscopy.
When laparoscopy is indicated
If there is evidence or a strong suspicion of endometriosis, pelvic or adnexal adhesions, or significant tubal disease, laparoscopy is warranted. It also may be helpful in younger patients (eg,
Because they reduce pregnancy rates by 50%, hydrosalpinges should be removed or the fallopian tube should be ligated proximally before IVF. It also is important to consider the number of patients needed to treat by laparoscopy to obtain 1 additional pregnancy.
Only gynecologists with expertise should perform laparoscopy, because it is important to make the correct diagnosis and be capable of surgically treating conditions found during the surgery.
Skip the postcoital test, but keep the semen analysis
Abnormalities of the cervical mucus or sperm–mucus interaction rarely cause infertility. Therefore, the postcoital test has questionable predictive value and is probably only useful to confirm that the couple can have properly timed intercourse during the cycle.3
A male factor is solely responsible in about 20% of infertile couples and contributory in another 30% to 40%. For this reason, semen analysis is always warranted when the female is being evaluated for infertility.
Examination of the male partner should be performed by the gynecologist, or the male should be referred to a urologist interested in infertility.6
For recurrent pregnancy loss, best treatment is TLC
Recurrent pregnancy loss is challenging because it is so emotionally charged for the patient, the cause is often unclear, and we lack specific treatments. A methodical and empathetic approach is therefore recommended.
What the history can reveal
Many women with recurrent pregnancy loss will eventually have a live birth, but increasing numbers of miscarriages do predict a poorer overall chance of success, as does increasing age.
Lifestyle factors rarely, if ever, cause recurrent pregnancy loss, but the following factors may increase the risk of miscarriage: obesity, high daily caffeine intake, alcohol consumption, use of nonsteroidal anti-inflammatory drugs, and social class and occupation. A previous diagnosis of or treatment for infertility also increases the risk of recurrent loss.
Smoking should be discouraged and healthy lifestyles should be promoted.7
Causes of recurrent pregnancy loss
Definite causal factors include chromosomal abnormalities, such as translocations, in approximately 5% of couples with 2 or more losses.
Probable factors include uterine abnormalities (both congenital abnormalities such as septate, and acquired defects such as adhesions and intrauterine or submucous myomas), uncontrolled thyroid disease or diabetes, PCOS, and antiphospholipid antibody syndrome.
Other thrombophilias, such as those associated with factor V Leiden mutation, activated protein C resistance, and possibly prothrombin G20210A and protein S deficiency, have been found by some investigators to be associated with recurrent pregnancy loss. It is doubtful that antithyroid antibodies and sharing of parental human lymphocyte antigen (HLA) cause recurrent miscarriage.7