The Role of Non-steroidal Anti-inflammatory Drugs in Natural Cycle IVF

Minimal Simulation and Natural Cycle In Vitro Fertilization, Allahbadia, G and Nitzschke, M, 2015

The Role of Non-steroidal Anti-inflammatory Drugs in Natural Cycle IVF (Voget, J and Nitzschke, M)

Dr Daiter’s summary of this chapter
Non-steroidal anti-inflammatory drugs (NSAIDs) can effectively delay or block follicle rupture around the time of ovulation, which may lower the risk of premature ovulation prior to oocyte (egg) retrieval.  “Genes encoding the progesterone receptor and cylco-oxygenase (COX-2) enzyme seem to be essential for ovulation.”  NSAIDs inhibit the formation of COX-2, which is one of the main enzymes that facilitates ovulation and they reduce prostaglandin production to prevent follicular rupture (release of the egg).  In one study comparing the odds of spontaneous ovulation prior to oocyte (egg) retrieval during natural cycle IVF demonstrated that cycles without Indomethacin (a NSAID) were 4 times more likely to ovulate prematurely than in cycles treated with Indomethacin.

The NSAIDs initial dose is the morning of a spontaneous LH rise (or when ovulation is triggered) and it is continued until the night before egg retrieval.

An example of one protocol: the initial serum LH + E2 levels can be evaluated on cycle day 10-11 and if LH is not elevated then it is repeated every 1-2 days until it rises; alternatively the ovulation can be triggered with a GnRH agonist when the follicle is mature in size and the E2 is greater than 250 pg/mL along with a low LH; NSAIDs (Ibuprofen 600-800mg every 8 hours) can be started when the LH rises or ovulation is triggered and is continued until the morning of egg retrieval (generally 48 hours after LH begins to rise, or 36 hours after the LH is greater than 30 IU/L, or 36 hours after ovulation trigger), embryo transfer is on post retrieval day 2-3 and luteal progesterone (progesterone 200mg vaginally daily) is given until the pregnancy test is positive.

An even more natural protocol: no ultrasound monitoring or serum LH monitoring is done until the patient detects the LH peak with commercially available ovulation predictor kits; when the LH is peak on home urine testing, then a serum level for LH + E2 is performed in order to schedule the time for egg retrieval.  This is highly convenient for patients and very inexpensive, but the embryo lab needs to be ready at all times since the timing of retrieval cannot be predicted or scheduled ahead of time (egg retrieval can be delayed for 1 day with the use of a GnRH antagonist) and statistically only about 50% of egg retrievals result in an embryo transfer (the pregnancy rate per embryo transfer is stated to be about 30%).

In these protocols, the patient is usually observed for at least one month prior to treatment to determine when ovulation generally occurs for that particular woman.  In one particular patient (with regular 26 day cycles), daily ultrasound and serum LH + E2 levels confirmed ovulation on CD 12, so the next cycle the woman was given 50mg Indomethacin every 12 hours starting on the morning of her 9th day, the 10th day serum E2 + LH were consistent with those of the prior cycle so she continued Indomethacin twice a day and at 9AM on the 12th day a 19mm follicle was identified and aspirated (a mature egg was retrieved).

Dr. Eric Daiter’s review of this chapter
Dr. Voget is a fertility expert in Brazil and Dr. Nitzschke is a fertility expert from Spain.

This is a useful chapter since it provides evidence that NSAIDs actually do perform fairly well to reduce the risk of premature ovulation prior to retrieval and it provides a variety of protocols that may be helpful in different clinical situations.

The information in this chapter is enough to encourage the regular use of NSAIDs to help prevent premature ovulation, increase the likelihood of retrieving a mature egg, allow embryo transfer, and increase the chance of a successful clinical pregnancy.



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