Ovulation induction

Ovulation induction
Intervention
MeSH	D010062

Ovulation induction is the stimulation of ovulation by medication. It is usually used in the sense of stimulation of the development of ovarian follicles^[1][2][3] to reverse anovulation or oligoovulation, but can also be used in the sense of triggering oocyte release from relatively mature ovarian follicles. In any case, ovarian stimulation (in the sense of stimulating the development of oocytes) is often used in conjunction with ("strict") ovulation induction.^[4] Also, a few definitions also include controlled ovarian hyperstimulation (stimulating the development of multiple follicles of the ovaries in one single cycle) in the definition of ovarian stimulation.^[4] Otherwise, ovarian hyperstimulation may still be a side effect of ovulation induction.

Reversing anovulation or oligoovulation

Ovulation induction in the sense of reversing anovulation or oligoovulation is indicated for women who do not ovulate on their own regularly,^[2] such as those with Polycystic ovary syndrome (PCOS).^[5] The medication which is most commonly used to treat anovulation is clomifene citrate (or clomid), which is a selective estrogen receptor modulator (SERM) that increases production of gonadotropins by inhibiting negative feedback from estrogen on the hypothalamus.

Also, where anovulation or oligovulation is secondary to another disease, the treatment for the underlying disease can be regarded as ovulation induction, by indirectly resulting in ovulation.

Final maturation and/or release

Ovulation induction can also refer to the induction of the final maturation of already relatively developed ovarian follicles and their oocytes, as well as triggering oocyte release from the ovary. Colloquially, this is known as the "trigger shot."^[6] This induction of final maturation and release of oocytes is the physiological role the LH surge by luteinizing hormone.

Administration of medication for triggering of oocyte release avails for sexual intercourse or intrauterine insemination to be scheduled at ovulation, the most likely time to achieve pregnancy.^[4] In in vitro fertilization, induction of final maturation avails for egg retrieval when the eggs are fully mature.

Medications used for final maturation and/or release of oocytes include:

• Human chorionic gonadotropin (HCG or hCG) in a low dose, which may be injected after completed ovarian stimulation. Ovulation will occur between 38 and 40 hours after a single HCG injection.^[7] It is also used in in vitro fertilization, where it makes the follicles perform their final maturation. A transvaginal oocyte retrieval is then performed at a time usually between 34 and 36 hours after hCG injection, that is, just prior to when the follicles would rupture. HCG injection confers a risk of ovarian hyperstimulation syndrome. Recombinant HCG (rHCG), recombinant luteinizing hormone (rLH) and urine-derived hCG (uHCG) are equally effective in achieving final follicular maturation in IVF with regards to pregnancy rates and risk of ovarian hyperstimulation syndrome.^[8] Therefore, urine-derived hCG (uHCG) is regarded as the best choice for final oocyte maturation triggering in IVF due to availability and cost.^[8]
• GnRH agonist, resulting in an elimination of the risk of ovarian hyperstimulation syndrome.^[9] In in vitro fertilization, the delivery rate is approximately 6% less than with hCG triggering.^[9] Using GnRH agonist for final maturation and/or release necessitates using a GnRH antagonist protocol for suppression of ovulation during ovarian hyperstimulation.

Risks & Side Effects

Ultrasound and regular hormone checks mitigate risks throughout the process. However, there are still some risks with the procedure. Medications used to induce ovulation can sometimes damage the lining of the uterus.

Ovarian Hyperstimulation Syndrome (OHSS) occurs in 5-10% of cases.^[10] Symptoms depend on whether the case is mild, moderate, or severe, and can range from bloating and nausea, through to shortness of breathe, pleural effusion, and excessive weight gain (more than 2 pounds per day).

There is also the risk that more than one egg is produced, leading to twins or triplets.

Alternatives

In vitro maturation is letting ovarian follicles mature in vitro, and this technique can potentially be an alternative both to anovulation reversal and oocyte release triggering. Rather, oocytes can mature outside the body, such as prior to IVF. Hence, no (or at least a lower dose of) gonadotropins have to be injected in the body.^[11] However, there still isn't enough evidence to prove the effectiveness and security of the technique.^[11]

References

1. Ovulation Problems and Infertility: Treatment of ovulation problems with Clomid and other fertility drugs. Advanced Fertility Center of Chicago. Gurnee & Crystal Lake, Illinois. Retrieved on Mars 7, 2010
2. Flinders reproductive medicine > Ovulation Induction Retrieved on Mars 7, 2010
3. fertilityLifeLines > Ovulation Induction Retrieved on Mars 7, 2010
4. IVF.com > Ovulation Induction Retrieved on Mars 7, 2010
5. Ovulation Problems and Infertility: Treatment of ovulation problems with Clomid and other fertility drugs Advanced Fertility Center of Chicago. Gurnee & Crystal Lake, Illinois
6. About.com
7. HCG Injection After Ovulation Induction With Clomiphene Citrate at Medscape. By Peter Kovacs. Posted: 04/23/2004
8. Farquhar, C.; Rishworth, J. R.; Brown, J.; Nelen, W. L. M.; Marjoribanks, J. (2013). Brown, Julie, ed. "Assisted reproductive technology: an overview of Cochrane Reviews". The Cochrane Library 8: CD010537. doi:10.1002/14651858.CD010537.pub2. PMID 23970457.
9. Humaidan, P.; Kol, S.; Papanikolaou, E.; Copenhagen GnRH Agonist Triggering Workshop Group (2011). "GnRH agonist for triggering of final oocyte maturation: time for a change of practice?". Hum. Reprod. Update 17 (4): 510–524. doi:10.1093/humupd/dmr008. PMID 21450755.
10. Ovulation Induction Risks and Overview
11. Vejledning om kunstig befrugtning 2006 (Danish)