Dr. Sher Blog

Official blog of Dr. Geoffrey Sher

Progesterone-Estrogen Hormonal Supplementation in IVF: How Does it Work and What is its Value?

by Dr. Geoffrey Sher on April 30, 2016

Ovulation occurs within 38-42 hours of initiation of the spontaneous luteinizing hormone (LH) surge (which can be detected in the blood or urine prior to this event) and/or hCG administered following controlled ovarian stimulation (COS) with gonadotropins.

One or more eggs are released with spontaneous or induced ovulation. Those follicles that ovulate and many of those emptied at egg retrieval, then undergo “luteinization”, converting to one or more a yellow bodies or corpora lutea (CL) that produces both progesterone and estrogen. The greater the original number of mature follicles, the greater the progesterone/estrogen production is likely to be. Accordingly, women on fertility drugs have higher luteal phase progesterone/estrogen levels.

The effect of the pre-ovulatory hCG injection is usually sustained for 1-2 weeks exerting a protracted influence on ovarian progesterone/estrogen production. A few days later, provided that embryo implantation takes place, the early trophoblast (root system of the conceptus) begins to produce its own progesterone/estrogen as well as hCG, in ever increasing amounts. By the 8th week of pregnancy the early placenta provides for all hormonal needs of the developing conceptus. There is compelling evidence to show that hCG augments ovarian (corpus luteum) progesterone release while also promoting growth and development of the trophoblastic “root system” of the conceptus (which eventually will develop into the placenta) as well as estrogen and progesterone production. Since, at the same time, hCG probably also promotes the production of more hCG, it might be considered to be a self-propagating hormone.

By the 8th-9th week of pregnancy, the trophoblast has replaced the ovaries as the dominant source of progesterone and estrogen production. Thereafter there is probably little or no benefit in supplementation with progesterone/estrogen It follows that a low blood progesterone blood level is much more likely to be the consequence rather than the cause of a failing pregnancy. Thus in such cases the administration of progesterone/estrogen in an attempt rescue a failing pregnancy is tantamount to “shutting the gate after the horse has left the stable.”

An obvious situation where progesterone/estrogen supplementation is required is in cases where the woman is an embryo recipient (i.e., ovum donation, embryo adoption, gestational surrogacy and frozen embryo transfers-FET).

By the 8th to 10th week of pregnancy, conversion from reliance upon the corpus luteum to sustain the pregnancy has occurred and further fetal development, supported by the hormonal production of the placental trophoblast. Thus thee is in my opinion little or no benefit in estrogen/progesterone supplementation beyond the 10th week.

While progesterone /estrogen supplementation likely has benefit in cycles involving pituitary down-regulation with GnRH agonists (e.g. Lupron, Buserelin, Superfact, Decapeptyl) or antagonist (Ganirelix, Orgalutron, Cetrotide) where luteal phase hormonal deficiency is more prevalent, there is no conclusive evidence that patients undergoing gonadotropin stimulation without the use of a GnRH agonist or an antagonist would derive benefit from such hormonal supplementation.

Hormonal supplementation usually involves the daily intramuscular administration of progesterone +/-  vaginal suppositories (comprising estradiol and micronized progesterone) until a blood pregnancy test is performed approximately eight days later (the chemical diagnosis of pregnancy). If the pregnancy test is negative or the plasma hCG levels fails to rise appropriately in the ensuing days, such hormonal support is discontinued. For those that cannot tolerate daily intramuscular progesterone, Crinone or Endometrin vaginal applications can be used instead.

Share this post:

17 comments

Leave A Reply
  • Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 5, 2018 reply

    I do not prescribe Estrace. discuss with your personal RE please!

    Geoff sher

  • Resh - January 30, 2018 reply

    Hello doc.
    I had done fet blastocyst on 22nd jan and underwent blood test yesterday. The readings of prog is 25 and e2 is 615. Pls advise if this reading is good enough. I am 41 years old and this is my 2nd ivf cycle. Had 5 good blastocyst which they have inserted 2 of yhem in this cycle.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 30, 2018 reply

    I would need to know the hCG level rather than E2 and progesterone to tell if you are implanting and likely to be pregnant.

    Geoff Sher

    Resh - January 30, 2018 reply

    Thanks for ur revertal. The doc has asked me to do bhcg on 5th feb. I am sure tat will show the actual results. I was quiet surprised why this blood test was done wen it doesnt give an idea of positive or negitve results. Wl revert bak as soon as i hv my reports. Tks n hv a great day ahed.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 30, 2018 reply

    Good luck!

    Geoff Sher

  • Jamie - January 12, 2018 reply

    This was a great article Dr. Sher. Many thanks! I love the level of detail you use. It’s really helpful.

    I have been looking and looking, but I can’t find an answer to this question so maybe you can enlighten me. I am 31 years old with no known issues (our infertility is male factor). We are gearing up for our first frozen cycle and my doctor has me on Estrace and Progesterone (vaginally) for 7 days until the end of my cycle, then I after stopping those I should get my period. Then I’ll call in my Day 1 and we’ll start prepping for a FET that cycle. My question is…why am I on anything at all this cycle when technically we’re taking a “break” between our egg retrieval (which was in December) and our FET (which will be in February). What is the purpose of taking both these meds if we’re not doing anything this month? Please help….this feels like such a technical question but I can’t find an answer!

    Jamie - January 12, 2018 reply

    I should add that originally we were going to head straight into a FET in January so they had me take Estrogen starting on my Day 1. But we changed out minds around about Day 8 and said that we would prefer to have a month off. Could having started Estrace on Day 1 be the reason they feel we must keep up the protocol this month, even if we’re not having a FET until the following month? (Thought I’d provide that info in case it’s relevant.)

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 12, 2018 reply

    Copy and yes…possible!

    Geoff Sher

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 12, 2018 reply

    As I see it the likely reason is to be able to launch and precisely time the treatment for your FET.

    Geoff Sher

  • Grace - November 11, 2017 reply

    Hi Dr. Sher,
    I just recently finished my first ivf cycle, to find out this afternoon that I am having a chemical pregnancy. I was taking 1 cc of PIO and 4 mg of Estrace. At 5 days past transfer, I went in to my dr for with bright red spotting, and when they ran my blood, they found that my progesterone levels were extremely low (20). This comes after my levels were in the thousands after my retrieval. My Dr upped me to 1.5 PIO, 3 days later my levels had raised a bit, bit the dr still has no idea why my body isn’t absorbing the PIO. He’s sure that this is the reason my pregnancy failed. I have heard of people getting PIO and suppositories, is this something that you would recommend? Any idea why my levels will not rise even with daily injections?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 11, 2017 reply

    In my opinion, a low progesterone is the consequence (rather than the cause) of a failing implantation.

    Geoff Sher

  • Cathy - March 3, 2017 reply

    EXCELLENT article, Dr. Sher!!!!! THANK YOU IMMENSELY!!!!!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - March 3, 2017 reply

    Thank you Kathy!

    Geoff Sher

  • Deborah - January 8, 2017 reply

    Dear Dr. Sher, I am almost 48 and preparing for my first ever FET using a 6 day BB blastocyst (PGD tested). I made the blast at age 44. This last year my cycles went from 27-28 days the first half of the year to most cycles now at 25 days, with a few 26, 27 or 29 days thrown in. I would rather not do a Lupron cycle. What would you recommend in my case? This is my last chance. Thanks

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 9, 2017 reply

    I personally would advise against natural cycle FET at your age. You need to use hormone therapy coming off a BCP in my opinion…whether you use Lupron overlap (which I believe to be preferable) or not.

    Frozen Embryo Transfer (FET): A frozen embryo transfer cycle is initiated by administering an oral contraceptive (OC) to the recipient. This is later overlapped with Lupron daily for 5-6 days. The OC is then withdrawn, but the daily Lupron injections are continued until the onset of menstruation. Next, the Lupron dosage is reduced and intramuscular (IM) estradiol valerate (Delestrogen) is administered every 3 days. The objective of the estradiol is to achieve and sustain an optimal plasma E2 concentration of 500pg/ml-1000pg/ml and a 9mm endometrial lining as assessed by ultrasound examination. Intramuscular and/or intravaginal progesterone is administered daily starting about 6 days prior to the FET and continued along with twice weekly IM Delestrogen until the 10th week of pregnancy or until it has been confirmed that the patient is not pregnant.
    Daily oral dexamethasone commences with the Lupron start and continues until a negative pregnancy test or until the completion of the 8th week of pregnancy. Then it is tapered down and discontinued. The recipient also receives prophylactic oral antibiotics starting with the initiation of Progesterone therapy, until the day after ET. Usually we would thaw vitrified blastocysts with the objective of having 1, 2 or 3 for transfer; depending on a couple’s stated preference. Commencing on the day following the ET, the patient inserts a vaginal progesterone suppository daily and this is continued until the completion of the 8th week of pregnancy or until a negative pregnancy test.
    As an alternative regimen for women who cannot tolerate intramuscular Progesterone (PIO), we prescribe either Crinone vaginal gel or Endometrin vaginal inserts according to protocol. If you’d like to explore one of these options, talk to your physician. For blastocyst FET’s, the blood pregnancy tests are performed 13 days and 15 days after the first progesterone administration is commenced.

    Good luck!

    Geoff Sher

  • Mark - September 13, 2016 reply

    In your opinion is it necessary to monitor progesterone levels after the 10th week mark with a normal ultrasound? How can one be certain that the placenta is producing the necessary amount to sustain the pregnancy?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 13, 2016 reply

    No ! Ordinarily there is no reason to do so in my opinion.

    Geoff Sher

Ask a question or post a comment