If you’re looking for better ways to treat infertility or enhance fecundity, here are some developments you’ll want to know about
IN THIS ARTICLE
Dr. Adamson is CEO of Advanced Reproductive Care Inc., and receives research support from IBSA.
The diagnosis and treatment of fertility are evolving rapidly as a result of clinical studies, scientific research, and changing socioeconomic and ethical perspectives. These developments benefit health-care consumers, but they also pose new challenges to general ObGyns and other practitioners committed to the best possible care for their patients.
In this Update, I focus on a number of these areas of change:
- care of women who have polycystic ovary syndrome (PCOS)
- the impact of myomas on fertility
- treatment of infertility in women who have endometriosis
- when tubal reconstruction is appropriate
- the impact of a woman’s age on fertility
- patient-friendly strategies to enhance fertility
- cross-border reproductive travel.
Use clomiphene citrate to stimulate ovulation in women who have PCOS
Practice Committee of the American Society for Reproductive Medicine. Use of insulin-sensitizing agents in the treatment of polycystic ovary syndrome. Fertil Steril. 2008;90(5 Suppl):S69–S73.
A new Committee Opinion from the American Society for Reproductive Medicine (ASRM) Practice Committee tackles the challenge of treating women with PCOS for infertility.
PCOS is associated with an increased risk of insulin resistance and diabetes mellitus. The first line of treatment for all women who have PCOS, especially those with an elevated body mass index, is lifestyle modification through diet and exercise, with the goal of losing weight.
Clomiphene is first-line therapy when ovulation is the aim
Metformin and other insulin-sensitizing agents may enhance ovulation and increase the response to clomiphene citrate in women who have PCOS and insulin resistance, but their use solely to enhance ovulation is unwarranted, and they do not reduce the rate of miscarriage. Clomiphene citrate should be the first-line treatment because it is much more effective. Long-term use of metformin to prevent disease is not advised.
Screen for insulin resistance at the time of diagnosis
Women who have PCOS should be given a 2-hour oral glucose tolerance test and have their lipid profile measured at the time of diagnosis and then at an interval of every 2 years. Insulin-sensitizing agents should be used for long-term health issues only after impaired glucose tolerance has been measured, if diet and exercise alone prove to be ineffective.
5-STEP TREATMENT OF ANOVULATORY INFERTILITY FOR WOMEN WHO HAVE PCOS
My strategy for stimulating ovulation in this population involves the following:
- Perform vaginal ultrasonography (US) on cycle day 3 for an antral follicle count and to rule out ovarian cysts >1 cm.
- Give clomiphene citrate, 50 mg, on cycle days 3 through 7 (or 5 through 9).
- Repeat vaginal US on cycle day 11 (or 13) to evaluate ovarian response. The optimal response is 1 to 2, and not more than 3, follicles ≥15 mm in size.
- Recommend timed intercourse, starting on cycle day 10 and then every 2±0.5 days until 1 to 2 days after ovulation.
- Measure urinary luteinizing hormone (uLH) daily, to detect uLH surge, starting on cycle day 11. A positive surge indicates that ovulation is likely within the next 12–48 hours. Absence of a surge indicates the likely absence of ovulation, which can be treated by giving 10,000 IU of human chorionic gonadotropin (hCG) subcutaneously or intramuscularly when the largest follicle is 18 to 25 mm in size.—G. DAVID ADAMSON, MD
When choosing a treatment for myoma, consider impacts on fertility
Practice Committee of the American Society for Reproductive Medicine in collaboration with the Society of Reproduction Surgeons. Myomas and reproductive function. Fertil Steril. 2008;90(5 Suppl): S125–S130.
A recent educational bulletin from the ASRM Practice Committee examined the relationship between myomas and reproductive function and reviewed management of this pathology.
The effects of myomas on reproductive outcome are ill-defined, but fibroids that distort the uterine cavity, as well as larger intramural myomas, may have adverse effects on fertility.
Select interventions carefully
Among women who have infertility and those who have recurrent pregnancy loss, myomectomy should be considered only after thorough evaluation. The reason? Postoperative adhesions as a result of abdominal myomectomy are common and may reduce subsequent fertility.
As for uterine artery embolization, myolysis, and MRI-guided ultrasonic treatment, these are not recommended for women who have myomas and who are seeking to maintain or improve fertility. The safety and efficacy of these procedures in this population have not been established.
Is a GnRH agonist useful?
Treatment of myomas with a gonadotropin-releasing hormone (GnRH) agonist does not improve fertility but may be helpful before surgery in anemic women and in those who might be able to undergo a less invasive procedure if the myoma volume were moderately smaller.
Adamson G. Management of endometriosis and infertility following surgery. In: Sutton C, Jones K, Adamson GD, eds. Modern Management of Endometriosis. London: Taylor & Francis; 2006:273–287.
New data make it easier to treat infertility in women thought to have endometriosis, although further randomized trials are needed. If other fertility variables are normal, and minimal to mild endometriosis is suspected but not confirmed, clomiphene citrate, 100 mg on cycle days 3 through 7, followed by intrauterine insemination (IUI) for 3 to 6 cycles, is a reasonable initial treatment, with the higher number of cycles being reserved for younger patients and those who have a better prognosis.
When is surgery helpful?
Diagnostic or operative laparoscopy, or both, is often indicated when one or more of the following are present:
- The patient experiences pain
- She fails to conceive after clomiphene citrate is administered and IUI is attempted for 3 to 6 cycles
- She has other factors associated with infertility.
If it is well performed, surgery is effective treatment for all stages of endometriosis, endometriomas, and disease of the cul de sac, for symptoms of pain or infertility, or both.
Generally, if pregnancy does not occur within 9 to 15 months after surgery, repeat surgery is of limited benefit for infertility, but may have some benefit for pain. In women who do not conceive after surgery, ovarian suppression for 2 months is of possible benefit before assisted reproductive technology (ART) and should be considered in patients who are also suffering from pain. Pre-ART surgery for large endometriomas is frequently indicated, and excision of the cyst capsule produces results superior to those of drainage, coagulation, or both.
After complete destruction of endometriosis in women who have infertility, ovarian suppression is not indicated. Rather, the patient should usually attempt to conceive for 9 to 15 months, with an outside range of 3 to 24 months for much older women who have an unfavorable prognosis, and for much younger women who have a good prognosis, respectively. If pregnancy does not occur, clomiphene citrate and IUI for 3 to 6 months are then indicated.
If this last strategy is unsuccessful, the options include:
- gonadotropins and IUI for 3 months to a maximum of 6 months in the young patient who has a good prognosis
- repeat laparoscopy (although this option is rare), possibly in conjunction with gamete intrafallopian transfer (GIFT), or, alternatively, in vitro fertilization (IVF). If the patient had a technically inadequate operation the first time, it sometimes is appropriate to repeat the surgery or go directly to IVF.
Practice Committee of the American Society for Reproductive Medicine. The role of tubal reconstructive surgery in the era of assisted reproductive technologies. Fertil Steril. 2008;90(5 Suppl):S250–S253.
In the era of ART, tubal reconstruction has fewer indications but is still appropriate and effective in properly selected individuals.
Determine the extent of tubal disease before reconstructive surgery
Hysterosalpingography is a useful initial test for the evaluation of tubal patency, but laparoscopy often is necessary to identify the nature and extent of pelvic disease. Selective salpingography or hysteroscopic tubal recanalization can help confirm the diagnosis of true proximal tubal occlusion.
Advise the patient of risks of surgery
Generally, the risk of ectopic pregnancy after tubal reconstruction is comparable to the risk of ectopic pregnancy associated with IVF, but the extent of tubal disease and pelvic pathology are important variables in predicting intrauterine and ectopic pregnancy rates.
The pregnancy rate after reversal of tubal sterilization depends on 1) the type of sterilization procedure that was performed, 2) site of anastomosis, and 3) postoperative tubal length, as well as 4) sperm quality and 5) the age of the female patient.
Maternal age, number of children desired, coexisting infertility variables, risk of ectopic and multiple pregnancy, and treatment cost are important considerations when counseling patients about the relative advantages and disadvantages of tubal surgery and IVF.
IVF is the best treatment for older women of reproductive age who have significant tubal pathology, and for women who have both proximal and distal occlusion.
Age, and duration of infertility, are key determinants of treatment
Committee on Gynecologic Practice of the American College of Obstetricians and Gynecologists, and Practice Committee of the American Society for Reproductive Medicine. Age-related fertility decline: a Committee Opinion. Fertil Steril. 2008;90(5 Suppl):S154–S155.
Women older than 35 years should receive expedited evaluation and treatment for infertility if they have not conceived after 6 months, or earlier if clinically indicated. That’s one of the conclusions from a recent ACOG–ASRM joint Committee Opinion on age-related fertility decline.
Age remains a major variable influencing a woman’s fertility and risk of pregnancy loss, and is increasingly important because of the social trend toward deferred child-bearing. The fertility rate peaks in a woman’s mid-20s and decreases by approximately 25% by age 35 and 50% by age 40, with a concomitant (and significant) increase in rates of aneuploidy and miscarriage.
The duration of infertility also is key. Of any given 100 women attempting to conceive:
- 78 will succeed within 1 year
- 88 will conceive within 2 years
- only an additional two or three women will conceive in the third year
- one more will conceive in each of the fourth and fifth years
- only three more will conceive over the rest of their reproductive life.
These data suggest that infertility should be investigated after 12 or more months of regular unprotected intercourse, with earlier evaluation and treatment for women who are older than 35 years.
Recurrent pregnancy loss and infertility are separate entities
By definition, recurrent pregnancy loss entails the loss of two or more pregnancies. When the cause is unknown, each loss merits careful review to determine whether specific evaluation may be appropriate. After three losses, thorough evaluation is warranted.1,2
To distinguish infertility from recurrent pregnancy loss, define clinical pregnancy as one documented by US or histopathology.
New technologies remain unproven
Although ovarian tissue and oocyte cryopreservation offer the promise of female fertility preservation, these technologies remain investigational to date.
Practice Committee of the American Society for Reproductive Medicine in collaboration with the Society for Reproductive Endocrinology and Infertility. Optimizing natural fertility. Fertil Steril. 2008;90(5 Suppl):S1–S6.
Another Committee Opinion from ASRM, in collaboration with the Society for Reproductive Endocrinology and Infertility, offers simple but effective steps for patients to take to optimize fertility. ObGyns should recommend these strategies to any woman planning to conceive in the near future.