# Luteal support
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{{Short description|Medication use in early pregnancy}}
'''Luteal support''' is the administration of medication, generally [progesterone](/source/progesterone), [progestin](/source/progestin)s, [hCG](/source/Human_chorionic_gonadotropin) or [GnRH agonist](/source/GnRH_agonist)s, to increase the success rate of [implantation](/source/Implantation_(human_embryo)) and early [embryogenesis](/source/Human_embryogenesis), thereby complementing and/or supporting the function of the [corpus luteum](/source/corpus_luteum). It can be combined with for example [in vitro fertilization](/source/in_vitro_fertilization) and [ovulation induction](/source/ovulation_induction).
Progesterone appears to be the best method of providing luteal phase support, with a relatively higher [live birth rate](/source/live_birth_rate) than placebo, and a lower risk of [ovarian hyperstimulation syndrome](/source/ovarian_hyperstimulation_syndrome) (OHSS) than [hCG](/source/Human_chorionic_gonadotropin).[{{cite journal|last1=Farquhar|first1=Cindy|last2=Marjoribanks|first2=Jane|title=Assisted reproductive technology: an overview of Cochrane Reviews|journal=[Cochrane Database of Systematic Reviews](/source/Cochrane_review)|volume=2018|article-number=CD010537|year=2018|issue=8|issn=1465-1858|doi=10.1002/14651858.CD010537.pub5|pmid=30117155|pmc=6953328}}] Addition of other substances such as estrogen or hCG does not seem to improve outcomes.[{{Cite journal | last1 = Van Der Linden | first1 = M. | last2 = Buckingham | first2 = K. | last3 = Farquhar | first3 = C. | last4 = Kremer | first4 = J. A. M. | last5 = Metwally | first5 = M. | title = Luteal phase support in assisted reproduction cycles | doi = 10.1093/humupd/dms017 | journal = Human Reproduction Update | volume = 18 | issue = 5 | page = 473 | year = 2012 | doi-access = free | hdl = 2066/98072 | hdl-access = free }}][{{Cite journal | last1 = Kyrou | first1 = D. | last2 = Kolibianakis | first2 = E. M. | last3 = Fatemi | first3 = H. M. | last4 = Tarlatzi | first4 = T. B. | last5 = Devroey | first5 = P. | last6 = Tarlatzis | first6 = B. C. | title = Increased live birth rates with GnRH agonist addition for luteal support in ICSI/IVF cycles: A systematic review and meta-analysis | journal = Human Reproduction Update | volume = 17 | issue = 6 | pages = 734–740 | year = 2011 | pmid = 21733980 | doi = 10.1093/humupd/dmr029| doi-access = free }}]
===Routes and formulations===
There is no evidence of any [route of administration](/source/route_of_administration) of progesterone or progestins being more beneficial than others for luteal support.
20 mg twice daily.[{{cite journal|last1=Rashidi|first1=Batool Hossein|last2=Ghazizadeh|first2=Mahya|last3=Tehrani Nejad|first3=Ensieh Shahrokh|last4=Bagheri|first4=Maryam|last5=Gorginzadeh|first5=Mansoureh|title=Oral dydrogesterone for luteal support in frozen-thawed embryo transfer artificial cycles: A pilot randomized controlled trial|journal=Asian Pacific Journal of Reproduction|volume=5|issue=6|year=2016|pages=490–494|issn=2305-0500|doi=10.1016/j.apjr.2016.10.002|doi-access=free}}]
|-
| [Progesterone](/source/Progesterone_(medication)) || 200 mg, 3-4 times daily[{{cite web|url=https://www.medscape.org/viewarticle/753218|title=Luteal Phase Progesterone Support in ART/IVF|author=Janelle Luk, MD|author2=Pasquale Patrizio|website=Medscape|access-date=2020-01-14}}]
|-
| [Desogestrel](/source/Desogestrel) || 450μg once per day.[{{cite journal|last1=Barbosa|first1=Marina Wanderley Paes|last2=Valadares|first2=Natália Paes Barbosa|last3=Barbosa|first3=Antônio César Paes|last4=Amaral|first4=Adelino Silva|last5=Iglesias|first5=José Rubens|last6=Nastri|first6=Carolina Oliveira|last7=Martins|first7=Wellington de Paula|last8=Nakagawa|first8=Hitomi Miura|title=Oral dydrogesterone vs. vaginal progesterone capsules for luteal-phase support in women undergoing embryo transfer: a systematic review and meta-analysis|journal=JBRA Assisted Reproduction|year=2018|issn=1518-0557|doi=10.5935/1518-0557.20180018|pmc=5982562|pmid=29488367|volume=22|issue=2|pages=148–156}}][{{cite journal|last1=Griesinger|first1=Georg|last2=Blockeel|first2=Christophe|last3=T. Sukhikh|first3=Gennady|last4=Patki|first4=Ameet|last5=Dhorepatil|first5=Bharati|last6=Yang|first6=Dong-Zi|last7=Chen|first7=Zi-Jiang|last8=Kahler|first8=Elke|last9=Pexman-Fieth|first9=Claire|last10=Tournaye|first10=Herman|title=Oral dydrogesterone versus intravaginal micronized progesterone gel for luteal phase support in IVF: a randomized clinical trial|journal=Human Reproduction|year=2018|volume=33|issue=12|pages=2212–2221|issn=0268-1161|doi=10.1093/humrep/dey306|pmid=30304457|pmc=6238366|doi-access=free}}]
*['''Intravaginal''' administration](/source/Intravaginal_administration) of gel, tablets or other inserts, such as [endometrin](/source/endometrin). A weekly [vaginal ring](/source/vaginal_ring) is an effective and safe method for intravaginal administration.[{{cite journal|last1=Stadtmauer|first1=Laurel|last2=Waud|first2=Kay|title=Progesterone Vaginal Ring for Luteal Support|journal=The Journal of Obstetrics and Gynecology of India|volume=65|issue=1|year=2014|pages=5–10|issn=0971-9202|doi=10.1007/s13224-014-0634-0|pmid=25737615|pmc=4342373}}]
*['''Intramuscular''' administration](/source/Intramuscular_administration). Daily intramuscular injections of progesterone-in-oil (PIO) have been the standard route of administration,[ but are not FDA-approved for use in pregnancy.
===Time of initiation===
The time for beginning luteal support can be put in relation to various events:
*In [IVF](/source/in_vitro_fertilization), generally somewhere between the evening of [oocyte retrieval](/source/oocyte_retrieval) and day 3 after oocyte retrieval, with weak evidence indicating that 2 days after oocyte retrieval may be optimal.][{{cite journal|vauthors=Connell MT, Szatkowski JM, Terry N, DeCherney AH, Propst AM, Hill MJ | title=Timing luteal support in assisted reproductive technology: a systematic review. | journal=Fertil Steril | year= 2015 | volume= 103 | issue= 4 | pages= 939–946.e3 | pmid=25638420 | doi=10.1016/j.fertnstert.2014.12.125 | pmc=4385437 }}]
*In [artificial insemination](/source/artificial_insemination), luteal support is generally started on the day of insemination, or 1 to 2 days after.[{{cite journal|last1=Green|first1=Katherine A.|last2=Zolton|first2=Jessica R.|last3=Schermerhorn|first3=Sophia M.V.|last4=Lewis|first4=Terrence D.|last5=Healy|first5=Mae W.|last6=Terry|first6=Nancy|last7=DeCherney|first7=Alan H.|last8=Hill|first8=Micah J.|title=Progesterone luteal support after ovulation induction and intrauterine insemination: an updated systematic review and meta-analysis|journal=Fertility and Sterility|volume=107|issue=4|year=2017|pages=924–933.e5|issn=0015-0282|doi=10.1016/j.fertnstert.2017.01.011|pmid=28238492|doi-access=free}}]
===Duration===
Luteal support given for a shorter duration than 7 weeks results in an increased risk of miscarriage in women with a dysfunctional [corpus luteum](/source/corpus_luteum) (as can be diagnosed by [blood test](/source/blood_test)s for endogenous progesterone).[{{cite journal|last1=Lien|first1=Y.R.|last2=Jou|first2=G.|last3=Yang|first3=P.|last4=Chen|first4=S.|title=The duration of luteal phase support by progesterone in fresh transfer cycles can be determined by corpus luteum rescue or not|journal=Fertility and Sterility|volume=104|issue=3|year=2015|pages=e344–e345|issn=0015-0282|doi=10.1016/j.fertnstert.2015.07.1074|doi-access=free}}] In general, however, luteal support can safely be discontinued at the time of a positive [pregnancy test](/source/pregnancy_test) (approximately 2 weeks after fertilization).[{{cite book|last1=Wiweko|first1=Budi|title=Ovarian Stimulation Protocols|chapter=Luteal Phase Support in Controlled Ovarian Hyperstimulation|year=2016|pages=135–144|doi=10.1007/978-81-322-1121-1_11|publisher=Springer|isbn=978-81-322-1120-4|chapter-url=https://books.google.com/books?id=_I6QCgAAQBAJ&pg=PA135}}]
==Other substances tested in luteal phase==
The addition of estrogen or hCG as adjunctives to progesterone do not appear to affect outcomes [pregnancy rate](/source/pregnancy_rate) and [live birth rate](/source/live_birth_rate) in IVF.[ [Low molecular weight heparin](/source/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.]