Infertility Challenges: Treatments & Health Implications

Pharmacy TimesJune 2013 Women's Health
Volume 79
Issue 6

The increase in the use of fertility-enhancing drugs has led to new health challenges caused by medication side effects and multiple births.

The increase in the use of fertility-enhancing drugs has led to new health challenges caused by medication side effects and multiple births.

One in 6 couples has trouble conceiving.1,2 The American Society for Reproductive Medicine (ASRM) recommends that couples who have trouble conceiving seek treatment after 1 year, and further advises couples 35 years or older to seek treatment after just 6 months of unprotected intercourse.3 Consequently, the use of fertility-enhancing drugs has increased exponentially over the last 3 decades. With this increase has come a new set of problems and challenges.


Causes of infertility can be identified in 70% of cases. Infertility specialists categorize problems as follows4:

  • Ovulation problems: one-fourth of all infertility problems are caused by the woman’s failure to ovulate predictably. Underlying causes include polycystic ovarian syndrome, insufficient pituitary hormone production, thyroid disease, and obesity or eating disorders.
  • Tubal and peritoneal factors: 35% of problems result from an inhospitable fallopian tube (where eggs are usually fertilized) or peritoneal (pelvis and abdomen lining) malfunctions that prevent egg implantation in the uterus.
  • Male infertility: 40% of cases are the result of suboptimal semen volume, poor sperm motility, or aberrant sperm morphology.2,4

Although these are the basic causes of infertility, contributing factors increase the likelihood of infertility. A significant factor is the fact that 20% of women wait until 35 years or older to start a family. Contributing dynamics include easy access to contraception since the 1960s, more women in the workforce, later marriage, high divorce rates, and delay until financially stability is achieved. Additionally, many women are unaware that fertility declines beginning in their late 20s (see Table 1). Sadly, pregnancy is then difficult when they are finally ready.5-8

Fertility specialists assess ovarian reserve in women using serum levels of follicle-stimulating hormone (FSH) and estradiol, an indicator of age-related fertility potential. Elevated FSH indicates a lower chance of pregnancy.9

The Solutions

Fertility clinics use several methods to help infertile couples become pregnant. The most common, intrauterine insemination, begins by having the woman take fertility drugs (see Table 2) to stimulate superovulation. At a carefully selected time, the physician inserts sperm into the uterus.11

In vitro fertilization (IVF), a different method costing about $12,000 per cycle, uses the woman’ s eggs (removed through the vagina with an ultrasound-guided needle, often after the use of ovarian stimulation drugs) and the man’s sperm to allow fertilization in the laboratory. Several or many embryos may result. The physician implants the resultant embryos—the number implanted is a judgment call—in the women's uterus. IVF risks include significant side effects from drugs, egg retrieval—related problems like injury to organs near the ovaries, ovarian bleeding, and pelvic infection. Additionally, the risk of multiple fetuses can cause premature labor or delivery, maternal hemorrhage, cesarean delivery, hypertension, and gestational diabetes.12

Multiple Births

Spontaneous pregnancies have a 1 in 90 chance of resulting in twins, and a very small chance of triplets or quadruplets. In 1966, physicians performed 64,481 IVF procedures in 330 clinics. In 1971, 29 of 100,000 live-born children were triplets or more. US triplet birth rates peaked in 1998, when 193.5 children per 100,000 live births were triplets or more. The triplet rate has since declined, but the twin rate has escalated. In 2009, physicians performed 134,260 IVF procedures in 483 clinics. Competition in this $1-billion industry is fierce, driving physicians to implant multiple embryos to ensure success. With no regulation, little insurance coverage, demanding patients, and poor patient education about the financial and emotional risks, multiple implants and births continue.13,15-18

The Concerns

Infants born as multiples are almost always premature, and have higher rates of low birth weight, cerebral palsy, developmental delays, and birth defects. Twins are 7 times—and triplets 20 times—more likely than singletons to die within a month of birth. A twin birth is 16 times more expensive than a singleton birth, and triplet or higher-order multiple birth can cost several hundred thousand dollars. Twins usually survive but are hospitalized twice as long as singletons, and have much higher medical costs over their first 5 years. After birth, the US health system picks up the tab, creating higher insurance premiums, hospital fees, and taxes to cover the treatment, education, and care of children with medical problems.13,15-19

When multiple embryos become viable fetuses and threaten the life of the mother or child, fertility specialists usually recommend selective reduction. It improves the chances that at least some of the children will be born healthy, and is usually performed between weeks 9 and 12 of gestation. One-third of infertile couples refuse selective reduction on religious or ethical grounds.20-22

Final Thought

Legislators and professional organizations encourage fertility doctors to reduce multiple births. The ASRM recommends transferring 1 embryo for women under the age of 35 years (and no more than 2, except in extraordinary circumstances), and a maximum of 5 for older women.23 Pharmacists who work with couples hoping to solve infertility issues using IVF should make sure they are fully aware of its risks and benefits.

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy and a freelance writer from Virginia.


  • Centers for Disease Control and Prevention. FastStats: infertility. Accessed February 15, 2013.
  • Kamel RM. Management of the infertile couple: an evidence-based protocol. Reprod Biol Endocrinol. 2010;8:21.
  • The American Society for Reproductive Medicine. Infertility: an overview. Accessed February 15, 2013.
  • Ray A, Shah A, Gudi A, Homburg R. Unexplained infertility: an update and review of practice. Reprod Biomed Online. 2012;24:591-602.
  • Forti G, Krausz C. Evaluation and treatment of the infertile couple. J Clin Endocrinol Metab. 1998;83(12):4177-4188.
  • Whitman-Elia GF, Baxley EG. A primary care approach to the infertile couple: clinical review. J Am Board Fam Pract. 2001;14:33-45.
  • Case AM. Infertility evaluation and management: strategies for family physicians. Can Family Physician. 2003;49:1465-1472.
  • Taylor A. ABC of subfertility: making a diagnosis. BMJ. 2003;327:494-497.
  • Practice Committee of the American Society for Reproductive Medicine. Aging and infertility in women. Fertil Steril. 2004;82(suppl 1):S102-S106.
  • Pal L, Santoro N. Age-related decline in fertility. Endocrinol Metab Clin North Am. 2003;32:669-688.
  • Haagen EC, Nelen WL, Adang EM, Grol RP, Hermens RP, Kremer JA. Guideline adherence is worth the effort: a cost-effectiveness analysis in intrauterine insemination care. Hum Reprod. 2013;28:357-366.
  • Zollner U, Dietl J. Perinatal risks after IVF and ICSI [published online Aug 18, 2012]. J Perinat Med.
  • van Heesch MM, Bonsel GJ, Dumoulin JC, et al. Long term costs and effects of reducing the number of twin pregnancies in IVF by single embryo transfer: the TwinSing study. BMC Pediatr. 2010;10:75.
  • Micromedex Healthcare Series [Internet database]. Greenwood Village, CO: Thomson Healthcare. Updated periodically. Accessed February 26, 2013.
  • Ismail L, Mittal M, Kalu E. IVF twins: buy one get one free? J Fam Plann Reprod Health Care. 2012;38(4):252-257.
  • Martin JR, Bromer JG, Sakkas D, Patrizio P. Insurance coverage and in vitro fertilization outcomes: a U.S. perspective. Fertil Steril. 2011;95:964-969.
  • Griffiths A, Dyer SM, Lord SJ, Pardy C, Fraser IS, Eckermann S. A cost-effectiveness analysis of in-vitro fertilization by maternal age and number of treatment attempts. Hum Reprod. 2010;25:924-931.
  • Chambers GM, Sullivan EA, Ishihara O, Chapman MG, Adamson GD. The economic impact of assisted reproductive technology: a review of selected developed countries. Fertil Steril. 2009;91:2281-2294.
  • Bakalar N. Regimens: use of 3 or more embryos is called too risky. NY Times. January 23, 2012. Accessed February 15, 2013.
  • Evans MI, Ciorica D, Britt DW, Fletcher JC. Update on selective reduction. Prenat Diagn. 2005;25:807-813.
  • O’Leary D. No room in the womb? couples with high-risk pregnancies face the ‘selective reduction’ dilemma. Christ Today. 1999;43:60-65.
  • Britt DW, Evans WJ, Mehta SS, Evans MI. Framing the decision: determinants of how women considering multifetal pregnancy reduction as a pregnancy-management strategy frame their moral dilemma. Fetal Diagn Ther. 2004;19:232-240.
  • The American Society for Reproductive Medicine. Fertility drugs and the risks of multiple births. Accessed February 15, 2013.

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