IVF is a meticulous process that involves many stages. From ovarian stimulation till embryo transfer, the lady has to undergo multiple closely monitored steps. Medicines play a crucial role in IVF.
In IVF cycle, the hormones of the body are tightly controlled by the fertility experts with the help of medicines. To understand it closely, we need to understand about woman’s menstrual cycle.
The Menstrual cycle began with the bleeding phase that last for 4-5 days. In this phases the small follicles of the ovary, also known as antral follicles start getting recruited. In a natural cycle, only one out of these recruited follicles attain dominance. Rest of the follicles undergo atresia. The dominant follicle produces a very important female hormone known as “Estrogen”. This estrogen in its active form acts on the uterine lining known as endometrium to prepare it for pregnancy. The dominant follicle is destined to ovulate around day 13-15 of the cycle. Once it gets ovulated, the dominant follicle becomes corpus luteum that produces “Progesterone”, another important hormone for pregnancy maintenance. In case of pregnancy, this corpus luteum is supported by the chemical known as hCG that is released from the embryonic tissue i.e. trophectoderm.
Pregnancy support after Ovulation induction and IUI
Ovulation induction can be done with clomephene citrate, letrozole, tamoxifene or gonadotropin injections. Pregnancy support in the luteal phase (phase after ovulation) is required after letrozole, tamoxifene and gonadatropin injections. However, pregnancy supporting medicines are not mandatory if ovulation induction is done with clomiphene citrate.
Pregnancy support after IVF
Pregnancy support is mandatory to continue in IVF pregnancies. Since the entire hormonal cycle is controlled exogenously, progesterone hormone need to supplemented from outside for a longer period of time, along with other adjunct medicines.
Type of Pregnancy supporting medicines
The main pregnancy supporting medicine is Progesterone. It is available in various formulations in the market.
- Natural micronised Progesterone
- Synthetic Progesterone like Dydrogesterone, hydroxyprogesterone caproate.
Other pregnancy supporting drugs of lesser use are hCG injection, Heparin, aspirin, GnRH agonist, GCSF, etc.
Route of administration
Progesterone can be administered:
- Orally
- Vaginally
- Sub-cutaneously
- Intra-muscularly
Natural micronised progesterone is available in capsule, tablet and injection formulations. Vaginal route of administration has better absorption rate, higher efficacy and has lesser side-effects as compared to oral route, however, some patients may complaint of irritation and vaginal discharge.
Intra-muscular route of administration has slower absorption rate, however, has longer duration of action. Intra-muscular injection is associated with side-effects like injection site pain, redness, etc.
Sub-cutaneous injections have early onset but lesser duration of action. Some patients may complain injection site pain. Only advantage of sub-cutaneous injection over intramuscular injection is that it is patient friendly, i.e. the lady may administer it herself. Intra-muscular injections require a healthcare personal to administer the injection in correct way.
Synthetic formulations of progesterone is available in tablet form (Dydrogesterone) and Intramuscular (hydroxyprogesterone caproate) injection.
Dydrogesterone was launched in the market for medical use in 1961. Dydrogesterone does not have any action on androgen, estrogen, glucocorticoid receptors. It does not interfere with follicular growth, corpus luteum formation and maintenance. It has higher oral absorption as compared to natural micronised progesterone.
Common side-effects of progesterone include fatigue, sedation, headache, urinary frequency, and jaundice related to intrahepatic cholestasis.
Dydrogesterone has been linked to increased incidence of congenital heart disease in a subpopulation of Palestine region.
The use of Hydroxyprogesterone caproate has been discouraged now a days, as it has been withdrawn by FDA due to its non effectiveness in preventing preterm deliveries.
Progesterone supplementation in IVF pregnancies
The IVF cycle is externally controlled by exogenous hormonal injections, and the aim is to produce multiple egg forming follicles. These multiple dominant follicles after ovum pick-up, form faulty corpus luteum which is responsible for maintaining pregnancy. Therefore, aggressive exogenous luteal support is required. In fresh embryo transfer cases, the luteal support is given with mainly progesterone and hCG injections. In frozen embryo transfer cases, the luteal support is given by estrogen and progesterone. The luteal support is mandatory for atleast 14 days, till the pregnancy test report comes positive. As the embryo-placental transition happens around 8 weeks, some clinicians prefer to continue luteal support till 8-10 weeks.
Conclusion
Progesterone support is mandatory after the use of ovulation inducting agents like letrozole, tamoxifene, and gonadotropin. Progesterone support is should be given aggressively in IVF cases upto atleast 8-10 weeks of period of gestation. Progesterone suuplementation can be given vaginally, orally and parentally (intra-muscular or sub-cutaneous), depending upon clinician’s choice and patient’s preference. Careful monitoring need to be done when progesterone is used for prolonged period of time, as it may increase the risk of intra-hepatic cholestasis of pregnancy.
Read more: Progesterone – Pregnancy supporting medicine
Dr Anadeep Chandi 
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