Luteal support is the administration of medication, generally progesterone, progestins or GnRH agonists, to increase the success rate of implantation and early embryogenesis, thereby complementing and/or supporting the function of the corpus luteum.
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The live birth rate is significantly higher with progesterone for luteal support in IVF cycles with or without intracytoplasmic sperm injection (ICSI). Co-treatment with GnRH agonists further improves outcomes, by a live birth rate RD of +16% (95% confidence interval +10 to +22%).
Formulations of progesterone or progestin
The main formulations of progesterone or progestins for luteal support are:
While daily intramuscular injections of progesterone-in-oil (PIO) have been the standard route of administration, PIO injections are not FDA-approved for use in pregnancy. A Cochrane review in 2015 stated that progesterone appears to be the best method of providing luteal phase support, but the evidence suggested the route of progesterone administration did not matter. A Cochrane review in 2011 found no evidence favoring a specific route of administration, dosage or duration of progesterone for luteal support.
Progestins used for luteal support include dydrogesterone and 17α-hydroxyprogesterone caproate
For egg donation, there is evidence of a lower pregnancy rate and a higher cycle cancellation rate when the progesterone supplementation in the recipient is commenced prior to oocyte retrieval from the donor, as compared to commenced day of oocyte retrieval or the day after.
Other substances tested in luteal phase
On the other hand, overall, the addition of estrogen or hCG as adjunctives to progesterone do not appear to affect outcomes pregnancy rate and live birth rate in IVF. In fact, luteal support with human chorionic gonadotropin (hCG) alone or as a supplement to progesterone has been associated with a higher risk of ovarian hyperstimulation syndrome (OHSS). The use of hCG should therefore be avoided for luteal support. Low molecular weight heparin as luteal support may improve the live birth rate but has substantial side effects and has no reliable data on long-term effects. Glucocorticoids such as cortisol do not seem to be effective for luteal support.