Luteal phase following controlled ovarian hyperstimulation for IVF is defective. Progesterone is the most commonly prescribed agent for luteal support. While more than 70% of physicians prescribe only vaginal progesterone, 17% combine progesterone with another agent.(1) Even progesterone only luteal phase support protocols can vary with regard to starting time, route of administration, dosage as well as stopping time. However, in a given clinic, usually there’s one luteal support protocol, which is given to all patients across the board. And even if there can be some modifications in the protocol according to the patient characteristics, the same protocol is followed until at least the day of pregnancy testing. It is a fact that only a minority of clinicians monitors their patients during the period between embryo transfer and pregnancy testing.
Based on the results of three prospective studies different luteal support protocols yield different serum progesterone levels (2,3,4). When 100 mg micronized progesterone is administered vaginally three times a day, three days after oocyte collection mean serum progesterone levels reach around 30 ng/ml with 95% of women having values between 10 and 50 ng/ml.(2). When 50 mg/day progesterone in oil was given intramuscularly mean serum progesterone levels were approximately 60 ng/ml, 95% of women had values between 15 and 100 ng/ml.(3) When 100 mg/day progesterone in oil was given intramuscularly mean serum progesterone levels were approximately 100 ng/ml and ranged between 20 – 25 ng/ml and over 150 ng/ml for 95% of women(4) Apparently different protocols yield very different serum progesterone levels, and even women on the same protocol can have serum progesterone levels in a wide range. Whether serum progesterone levels reflect endometrial progesterone levels is questionable, but in a secondary analysis of a randomized controlled trial comparing vaginal versus intramuscular progesterone for luteal support, a positive linear relationship between serum progesterone levels and the clinical pregnancy rate, regardless of the route of administration, was found.(4) Although this does not necessarily demonstrate a causal relationship it is still a noteworthy finding and can be used for generating a new hypothesis. It seems reasonable to think that luteal phase serum progesterone levels can be monitored and if it falls below some pre-determined threshold the dosage adjusted to increase the likelihood of a clinical pregnancy. To the best of my knowledge there’s no such study in the literature. We have designed a randomized controlled trial to test this hypothesis and it is awaiting ethics committee approval at the time of writing. The idea is to monitor serum progesterone levels one week after oocyte collection and increasing progesterone dosage if serum levels are less than 30 ng/ml.
References:
- 1. IVF-WorldWide.com - Results - An updated survey on the use of progesterone for luteal phase support in stimulated IVF cycles
- IVF-WorldWide.com Website
- 2. Friedler et al. Luteal phase characteristics following GnRH antagonist or agonist treatment – a comparative study.
- RBM 2006;12:27
- 3. Fauser et al. Endocrine Profiles after Triggering of Final Oocyte Maturation with GnRH Agonist after Cotreatment with the GnRH Antagonist Ganirelix during Ovarian Hyperstimulation for in Vitro Fertilization.
- JCEM 2002; 87:709
- 4. Mitwally et al. Vaginal micronized progesterone versus intramuscular progesterone for luteal support in women undergoing in vitro fertilization–embryo transfer.
- Fertil Steril 2010; 93: 554
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