Methodology

A range of fertility medication is available for women, who suffer from ovulation disorders or are considering undergoing fertility treatment. The medication will further enhance their probabilities to conceive, by causing the release of reproductive hormones that either trigger or regulate ovulation.

Types of Medications

Clomiphene Citrate (CC)

CC is structurally similar to oestrogen and binds to oestrogen receptors in the reproductive system. This reduces negative oestrogen feedback triggering normal compensatory mechanisms that alter the pattern of gonadotropin-releasing hormone (GnRH) secretion and stimulate increased pituitary gonadotropin release which, in turn, drives ovarian follicular development1.

Owing to its mechanism of action, Clomiphene citrate is approved for use in women with anovulation and has been used as a first line ovulation induction agent for over 40 years. There is high-quality evidence that clomiphene citrate is better than a placebo for ovulation and pregnancy rates, thus providing confidence for recommending use of clomiphene citrate as first line therapy2.

Even, for women with unexplained infertility, clomiphene citrate appears to be a sensible first choice treatment, given the low cost and ease of administration3. CC treatment will successfully induce ovulation in approximate 80% of properly selected candidates4. Half of them would get pregnant depending on the different other factors like age and male factor infertility4.

Clomiphene citrate is administered orally, typically starting on the third to fifth day after the spontaneous or progestin-induced menses; with starter dose of single 50 mg tablet daily for 5 consecutive days, increasing by 50 mg increments in subsequent cycles until ovulation is induced5. CC treatment is should be generally limited to minimum effective dose and to no more than six ovulatory cycles6.

Side Effects

  • CC is generally well tolerated. Hot flushes are one of the most common side effects, which typically disappear after treatment ends.
  • Mood swings, blurred or double vision, scotomata, light sensitivity is relatively uncommon and reversible7. Multi-follicular development, resulting in multiple gestation is considered as a principle risk of CC treatment (<10%)7.
  • A few scientific evidences suggest the use of fertility drugs increases the chance that a woman will develop ovarian cancer later in her life7. 
  • A few authors concluded the risk is higher for women who never get pregnant or failed to pregnant after many cycles of treatment6. Despite of these studies, association between CC use and possible ovarian cancer risk is not yet clearly determined6.

Gonadotropins and Human Chorionic Gonadotropin (HCG)

If clomiphene doesn’t work or a candidate is not suitable for CC, gonadotropin serves as a second choice. Gonadotropins include several different types of drugs that contain either a combination of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), or only FSH12. These hormones directly stimulate the ovaries to produce multiple follicles12. Gonadotropins are injected starting on day 2 or day 3 of the menstrual cycle for 7 to 12 days.

Human Chorionic Gonadotropin (HCG) is widely recognized for its role in ovulation and the support of early pregnancy14. In women, Chorionic gonadotropin human is used in the treatment of infertility or as part of a treatment programme for assisted reproduction. It exerts actions almost the same as those of luteinizing hormone (LH), which is produced by the pituitary gland15.

Independently of FSH, low-dose HCG can support development and maturation of larger ovarian follicles, potentially providing effective and safer ovulation induction regimens16. HCG seems to be capable of improving uterine receptivity by enhancing endometrial quality and stromal fibroblast function16.

Side Effects

  • The chance of a multiple birth is higher with gonadotropins than with clomiphene, and 30% of women who conceive a pregnancy with this medication have multiple births. About two-thirds of multiple births are twins. Triplets or larger multiple births account for the remaining third18
  • The most serious complication with super-ovulation is ovarian hyperstimulation syndrome (OHS), which is associated with the enlarged ovary (although the precise cause is unknown)12. This can result in dangerous fluid and electrolyte imbalances and endanger the liver and kidney. OHS is also associated with a higher risk for blood clots. In rare cases, it can be fatal. Symptoms include abdominal bloating, nausea, vomiting, and shortness of breath12.
  • Overproduction of follicles, if unchecked, may result in bleeding and rupture of ovarian cysts.

Bromocryptine or Cabergoline

Hyperprolactinaemia causes infertility in up to one-third of women with reproductive disorders21. Both drugs act as a dopamine receptor agonist, functioning like the prolactin inhibitory factor in the hypothalamus, to stimulate inhibitory dopamine receptors22. This results in prolactin release being inhibited and growth hormone release being modestly stimulated. Women with hyper-prolactinaemia are frequently prescribed dopamine agonists to reduce prolactin levels and restore normal menses21. Fertility and cyclical ovarian function are usually restored within two months22.

Bromocryptine or Cabergoline allow 90% of women to have normal prolactin levels25. Once prolactin levels become normal, 85% of women using Bromocryptine or Cabergoline will ovulate.13

Side Effects

  • Commonly reported side effects are nausea, dizziness, postural hypotension and headache.

Cabergoline is usually administered at doses ranging between 0.5 and 1.5 mg once or twice per week and preferred over Bromocryptine because of patient compliance and better tolerability26.

Cost

Clomiphene pills cost at least $50 a month (not including the cost of doctors’ visits, ultrasounds of the ovaries, or follow-up procedures such as artificial insemination. Gonadotropin injections cost £1,500 to £3,000 a month including doctors’ visits and tests.

Side Effects

Some of the side effects include hot flashes, cramping, bloating, vaginal dryness and headaches.

Bibliography

  1. https://www.inkling.com/read/clinical-gynecologic-endocrinology-infertility-8th/chapter-31/clomiphene-citrate by Marc A. Fritz and Leon Speroff. 8th edition published by Wolters Kluwer. Last accessed on October 9,2014”
  2. Misso ML et.al. Hum Reprod Update. 2013 Jan-Feb;19(1):2-11“
  3. Hughes E et al. Cochrane Database Syst Rev. 2000;(3):CD000057”
  4. Fertility and sterility, vol.86, suppl 4, November 2006”
  5. Fertility and sterility, vol.86, suppl 4, November 2006”
  6. Tomao et al. Journal of Ovarian Research 2014, 7:51”
  7. Fertility and sterility, vol.86, suppl 4, Novemeber 2006”
  8. Fertility and sterility, vol.86, suppl 4, Novemeber 2006”
  9. Fertility and sterility, vol.86, suppl 4, Novemeber 2006”
  10. Tomao et al. Journal of Ovarian Research 2014, 7:51”
  11. Tomao et al. Journal of Ovarian Research 2014, 7:51”
  12. Infertility in women, University of Maryland Medical Center, http://umm.edu/health/medical/reports/articles/infertility-in-women last accessed on October 9, 2014”
  13. Infertility in women, University of Maryland Medical Center, http://umm.edu/health/medical/reports/articles/infertility-in-women last accessed on October 9, 2014”
  14. Choi J et al. Mol Cell Endocrinol. 2014 Mar 5;383(1-2):203-13”
  15. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0000408/ last accessed on October 9, 2014”
  16. Filicori M et al. Fertil Steril. 2005 Aug;84(2):275-84.”
  17. Filicori M et al. Fertil Steril. 2005 Aug;84(2):275-84.”
  18. American Society for Reproductive Medicine. (2012). Medications for inducing ovulation. Retrieved June 11, 2012, from http://www.asrm.org/Medications_for_Inducing_Ovulation/”
  19. Infertility in women, University of Maryland Medical Center, http://umm.edu/health/medical/reports/articles/infertility-in-women last accessed on October 9, 2014”
  20. Infertility in women, University of Maryland Medical Center, http://umm.edu/health/medical/reports/articles/infertility-in-women last accessed on October 9, 2014”
  21. Shahdokht Motazedia etal. Indian J Med Res 131, May 2010, pp 670-674”
  22. “Neonatal Formulary 4, July 2004 http://www.neonatalformulary.com/pdfs/archive/bromocriptine.pdf Last accessed on October 9, 2014.”
  23. Shahdokht Motazedia etal. Indian J Med Res 131, May 2010, pp 670-674”
  24. “Neonatal Formulary 4, July 2004 http://www.neonatalformulary.com/pdfs/archive/bromocriptine.pdf Last accessed on October 9, 2014.”
  25. Fertility Treatments for Females http://www.nichd.nih.gov/health/topics/infertility/conditioninfo/Pages/treatments-women.aspx Last accessed on October 9, 2014.”
  26. “Al-Husaynei et al. Middle East Fertility Society Journal Vol. 13, No. 1, 2008”
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