Clinical Review


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The state of the art in 5 key areas, with recommendations from ASRM and other experts



The treatment of infertility has advanced rapidly over the past 25 years, thanks to technological developments and improved application of evidence-based clinical algorithms. Many tests and treatments that once were common no longer are, while rising in vitro fertilization (IVF) success rates and other laboratory procedures have transformed many aspects of management.

Changes are occurring so quickly it is often difficult for the general ObGyn to know the most advanced and appropriate treatment for a given patient. The American Society for Reproductive Medicine (ASRM) Practice Committee establishes guidelines based upon well-designed studies to help physicians keep abreast of the best clinical practices. In this article, I focus on recent ASRM guidelines in 5 topical areas associated with substantial misinformation in both the professional and public sectors:

  • when and how gynecologists should initiate infertility testing and treatment
  • how to evaluate and manage recurrent pregnancy loss
  • the need to reduce the rate of multiple gestation from IVF and ART
  • the expanded applications for preimplantation genetic diagnosis
  • the truth about fertility-sparing efforts in young women planning to undergo cancer therapy and other treatments.

When and how to evaluate patients complaining of infertility

Infertility is a disease, but there are different opinions about when a woman reporting this condition should be assessed (TABLE 1). According to the ASRM, a couple should not be considered infertile until they have tried to conceive spontaneously for at least 12 months, unless the medical history and physical findings dictate earlier evaluation and treatment.1

For example, approximately 25% of couples experience infertility when the woman is age 35, and about 50% experience it when the woman is age 40. Therefore, it is reasonable to investigate infertility after 6 months of attempted conception when the woman is over 35 and after 3 months if she is over age 40.2 The primary reason for this age-related reduction in fertility is the diminishing number and quality of oocytes over time.

Other risk factors for infertility include smoking, family history of premature ovarian failure, significant ovarian pathology, previous ovarian surgery, history of oligomenorrhea or amenorrhea, known or suspected disease of the uterus or fallopian tubes, endometriosis, or a partner known to be subfertile.3,4


When to investigate infertility, treat, and refer

After 12 months of unprotected intercourse if age
After 6 months of unprotected intercourse if age 35–39
After 3 months of unprotected intercourse if age ≥40
After 0–6 months if patient has history of or risk factors for infertility
Treat identifiable causes of infertility
Optimize factors influencing fertility:
  • Diet, weight, exercise
  • Timed intercourse
Treat empirically (eg, clomiphene, insemination) for 3–6 months in patients
History of infertility or significant risk factors
Significant fertility problems identified during investigation
Age ≥40
After 3–6 months of failed treatment for identifiable causes
After 3–6 months of failed empiric treatment

How to evaluate ovarian function

A careful history and physical examination are key components of systematic, expeditious, and cost-effective identification of the cause of infertility (TABLE 2). A menstrual history and basal body temperature recordings are useful in the diagnosis of ovulatory dysfunction and are easy to obtain. Measurements of urinary luteinizing hormone (LH) using ovulation-prediction kits and mid-luteal-phase serum progesterone are also helpful.

Endometrial biopsy is rarely indicated because of its lack of clinical relevance.

Serial vaginal ultrasonography of the size and number of ovarian follicles may be indicated when simpler methods are inconclusive.

Other tests to evaluate ovarian function may include thyroid-stimulating hormone (TSH), serum prolactin, cycle day 3 follicle-stimulating hormone (FSH) and estradiol, and the clomiphene citrate challenge test in selected patients at higher risk of ovarian dysfunction.


Current status of tests and treatments

Postcoital test
Endometrial biopsy
Antisperm antibodies testing
Intracervical insemination
Clomiphene for more than 3–6 cycles
Routine hCG injection to stimulate ovulation in clomiphene cycles
Clomiphene citrate challenge test in selected patients
Serial vaginal ultrasounds to evaluate response to ovarian stimulation
Saline sonohysterography
Preimplantation genetic diagnosis for single-gene defects
Embryo cryopreservation
Single-embryo transfer to reduce multiple pregnancy rates
Preimplantation genetic screening for aneuploidy in older patients
Human lymphocyte antigen typing for recurrent pregnancy loss
Intravenous immunoglobulin for recurrent pregnancy loss
Ovarian tissue or oocyte cryopreservation for fertility preservation
* Should be performed only in clinical trials


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