Luteal support

Luteal support is the administration of medication, generally progesterone, progestins, hCG or GnRH agonists, to increase the success rate of implantation and early embryogenesis, thereby complementing and/or supporting the function of the corpus luteum.

Progesterone appears to be the best method of providing luteal phase support, with a relatively higher live birth rate than placebo, and a lower risk of ovarian hyperstimulation syndrome (OHSS) than hCG.[1] Addition of other substances such as estrogen or hCG does not seem to improve outcomes.[1]

Progesterone and progestins

The live birth rate is significantly higher with progesterone for luteal support in IVF cycles with or without intracytoplasmic sperm injection (ICSI).[2][1] Co-treatment with GnRH agonists further improves outcomes,[1] by a live birth rate RD of +16% (95% confidence interval +10 to +22%).[3]

Formulations

There is no evidence of any route of administration of progesterone or progestins being more beneficial than others.[1] The main formulations of progesterone or progestins for luteal support are:

  • Vaginal gel, tablets or other inserts for intravaginal administration, such as endometrin. This was the most commonly used medication for luteal support in an Israeli survey in 2013, used without adjunctive medication in 77% of cases, mainly as tablets.[4]
  • Formulations for intramuscular administrations

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.

Progestins used for luteal support include dydrogesterone and 17α-hydroxyprogesterone caproate.[5]

Timing

Initiation of luteal support in IVF is generally somewhere between the evening of oocyte retrieval and day 3 after oocyte retrieval, with weak evidence indicating that 2 days after oocyte retrieval may be optimal.[6]

Duration of luteal support, in an Israeli survey in 2013, was generally until 8–10 weeks of gestational age or beyond.[4] Having a shorter duration than 7 weeks results in an increased risk of miscarriage in women with a dysfunctional corpus luteum (as can be diagnosed by blood tests for endogenous progesterone).[7]

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.[1] 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).[2] 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.[1] Glucocorticoids such as cortisol has limited evidence of efficacy as luteal support.[1]

References
  1. Farquhar, Cindy; Marjoribanks, Jane (2018). "Assisted reproductive technology: an overview of Cochrane Reviews". Cochrane Database of Systematic Reviews. 8: CD010537. doi:10.1002/14651858.CD010537.pub5. ISSN 1465-1858. PMC 6513476. PMID 30117155.
  2. Van Der Linden, M.; Buckingham, K.; Farquhar, C.; Kremer, J. A. M.; Metwally, M. (2012). "Luteal phase support in assisted reproduction cycles". Human Reproduction Update. 18 (5): 473. doi:10.1093/humupd/dms017.
  3. Kyrou, D.; Kolibianakis, E. M.; Fatemi, H. M.; Tarlatzi, T. B.; Devroey, P.; Tarlatzis, B. C. (2011). "Increased live birth rates with GnRH agonist addition for luteal support in ICSI/IVF cycles: A systematic review and meta-analysis". Human Reproduction Update. 17 (6): 734–740. doi:10.1093/humupd/dmr029. PMID 21733980.
  4. Vaisbuch, Edi; de Ziegler, Dominique; Leong, Milton; Weissman, Ariel; Shoham, Zeev (2014). "Luteal-phase support in assisted reproduction treatment: real-life practices reported worldwide by an updated website-based survey". Reproductive BioMedicine Online. 28 (3): 330–335. doi:10.1016/j.rbmo.2013.10.022. ISSN 1472-6483. PMID 24447959.
  5. Loose, Davis S.; Stancel, George M. (2006). "Estrogens and Progestins". In Brunton, Laurence L.; Lazo, John S.; Parker, Keith L. (eds.). Goodman & Gilman's The Pharmacological Basis of Therapeutics (11th ed.). New York: McGraw-Hill. pp. 1541–71. ISBN 978-0-07-142280-2.
  6. Connell MT, Szatkowski JM, Terry N, DeCherney AH, Propst AM, Hill MJ (2015). "Timing luteal support in assisted reproductive technology: a systematic review". Fertil Steril. 103 (4): 939–946.e3. doi:10.1016/j.fertnstert.2014.12.125. PMC 4385437. PMID 25638420.
  7. Lien, Y.R.; Jou, G.; Yang, P.; Chen, S. (2015). "The duration of luteal phase support by progesterone in fresh transfer cycles can be determined by corpus luteum rescue or not". Fertility and Sterility. 104 (3): e344–e345. doi:10.1016/j.fertnstert.2015.07.1074. ISSN 0015-0282.
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