Progesterone in IVF

Speaker: Dr. Gunjan Gulati, Laparoscopic Surgeon & IVF specialist, Ghaziabad

Expert: Dr. Archana Sharma, Laproscopic Surgeon, Scientific & Clinical Director Ganesh Hospital & Test-Tube Baby Centre Ghaziabad, Secretary West UP chapter ISOPARB, President Elect Ghaziabad Obs Gyn Society

Many contributing factors for progesterone supplementation:

1. In IVF cycles high level of hormones supplemented for follicular development, leads to higher estrogen which in turn sends negative feedback to HP Axis causing depletion in the LH. Thus more estrogen leads to lesser LH surge & for a shorter duration - so low midluteal LH levels, there is premature luteolysis and so less progesterone and LPD. Exogenous progesterone needs to be supplemented as endogenous progesterone is very low in these patients. In contrast, in a natural cycle there is optimum follicular development and adequate luteal function and the function of corpus luteum is maintained.

2. Corpus luteum is not maintained in IVF patients due to the use of GnRH analogues in IVF which causes negative feedback to HPA so low LH surge and LPD.

• Additional progesterone is important for maintenance of a functional secretory endometrium which in turn helps in a normal implantation & growth of the embryo so pregnancy is sustained.

• Abnormal low levels of LH can also lead to a miscarriage so progesterone supplementation is needed.

• Luteal Phase Support can be done with Progesterone, Estrogen, HCG, GnRH.

• The actions of Progesterone for LPS are–makes the endometrium (secretory) sticky to receive the embryo; increases endometrial vascularity, inhibits myometrial contractility, promotes uterine quiescence, stimulates uterine growth and immunomodulatory activity with TH2 increased & NK cells decreased–all this to achieve a healthy pregnancy.

• There are different formulations of progesterone–vaginal being the most favorite route with the IVF specialists; intramuscular (aqueous & oil based); and in case of oral-Dydrogesterone is more preferred due to better bioavailability, potency, compliance, immunomodulatory effect, live birth rates.

• Vaginal micronized progesterone is the favorite as it bypasses the first pass metabolism and higher concentration of progesterone reaches the uterus directly.

• There is no evidence that one treatment regimen is superior to the other, however practically in an IVF cycle there is supplementation with combination - one injectable progesterone, with vaginal preparation and / or oral progesterone like Dydrogesterone.

• Most clinicians do not end the progesterone support at luteal phase as stated by ASRM but continue the support till at least 8-12 gestational weeks.