Why is Progesterone Used for IVF?

Thank you Kami for the question.

In a natural cycle, progesterone is made by the corpus luteum(CL)(see blog from August 17, 2007). In most cases it’s just one, and for many millions of women around the world, this one little CL puts out enough progesterone get the job done. During IVF, there are usually many more than one CL, and therefore one might expect that there should be plenty of extra progesterone produced and available for the pregnancy. So why give more? There are 2 reasons.

The first is that the natural CL and the extra CLs that are produced during ovulation induction with insemination are different than the CL of IVF. The CLs of IVF were all disturbed by the IVF needle. The CLs from IVF all started as follicles containing eggs. At the retrieval, the needle is placed into the follicle, the egg is removed, and other cells can also be removed. The follicle is mostly fluid, but it also contains tons of cells that make up the follicle and surround the egg. These are called the granuslosa cells, and these are the cells that convert to progesterone CL cells after ovulation. So if the needle removes some of these cells, as is usually the case, the CL may not work as well and less progesterone would be produced.

The second has to do with the IVF medications. The CL makes the hormone progesterone, but the CL needs a hormone to help it perform this function. Leutinizing Hormone(LH) is the one. Yes the famous LH, of the LH surge. LH comes from the pituitary gland, and it is produce in high amounts just before ovulation to get ovulation to occur. (for IVF we use the LH substitute hCG, just to help with the timing). After ovulation, LH comes from the pituitary gland, in smaller amounts, to “leutinize” the follicle, or to get it to make the progesterone. LH is secreted throughout the luteal phase to keep the CL making progesterone. If a pregnancy occurs, the hCG from the pregnancy takes over to stimulate the CL progesterone system. If there is a problem with LH production in the luteal phase, there will be a problem with progesterone production and there will be a problem with the pregnancy.

Almost all women who undergo IVF are given a medication that causes a problem for LH production. Whether it’s Lupron or Antagon, LH production stops. Sounds bad? No it’s good, at least initially. Stopping LH means preventing a premature LH surge, which can ruin 10% of IVF cycles. In a natural pregnancy, or when doing iui, surges are fine, they cause ovulation. In IVF, we need to time the retrieval to the hour, so that a surge at the wrong time ruins everything. Therefore, we give medications to stop LH, but what they do is stop LH for a while, and this compromises the ability of the to make progesterone.

So there you have it. Progesterone may be lower than normal during IVF for 2 reasons. The second is probably more important than the first. That is, if we didn’t use the Lupron or Antagon, progesterone production would be fine for most women doing IVF. There are so many CL during IVF, a little needle disruption may not be a big deal.
Dr. Licciardi

References:

  • van der Linden M, Buckingham K, Farquhar C, Kremer JA, Metwally M. Luteal phase support in assisted reproduction cycles. Cochrane Database Syst Rev. 2011 Oct 5 ;(10):CD009154.
  • Licciardi FL, Kwiatkowski A, Noyes NL, Berkeley AS, Krey LL, Grifo JA. Oral versus intramuscular progesterone for in vitro fertilization: a prospective randomized study. Fertil Steril. 1999 Apr; 71(4):614-8.
  • Feinberg EC, Beltsos AN, Nicolaou E, Marut EL, Uhler ML. Endometrin as luteal phase support in assisted reproduction. Fertil Steril. 2012 Nov 5. pii: S0015-0282(12)02238-8. doi: 10.1016/j.fertnstert.2012.09.019. [Epub ahead of print]
  • Engmann L, DiLuigi A, Schmidt D, Benadiva C, Maier D, Nulsen J. The effect of luteal phase vaginal estradiol supplementation on the success of in vitro fertilization treatment: a prospective randomized study. Fertil Steril. 2008 Mar; 89(3):554-61.