NSAID
Route of administration
Dose
Data
Indomethacin
Rectal suppositories
50 mg 8/8 h
Kadoch et al. (2008)
Diclofenac
Rectal suppositories
25 mg 6/6 h
Kawachiya et al. (2012)
Ibuprofen
Oral capsules
600–800 mg 8/8 h
Uhler et al. (2001)
The NSAIDs first dose starts from the morning of LH rise or at the time of trigger injection, until the night before egg retrieval.
Here is an example for a protocol using Ibuprofen 600 mg/8 h:
The patient does her very first hormonal assay on her day 10 or 11 of cycle: E2 + LH. If LH surge is not seen on this first test, it should be repeated 1 or 2 days later, until LH surge is seen. Alternatively, it is also possible to induce ovulation with gonadotropin-releasing hormone (GnRH) analogs 0.1 mg injection, if E2 > 250 pg/mL without an LH surge. In this case, we already have a mature follicle, but LH surge has not started yet. From the day of LH surge or ovulation induction, a treatment with Ibuprofen 600 mg/8 h should be started, until the morning of egg retrieval. The egg retrieval should be performed 48 h after LH surge is seen or 36 h after ovulation induction. If on the day of hormonal assay, LH was already >30 IU/L, the egg retrieval should be done 36 h after LH surge is seen, instead of 48 h. A fresh embryo transfer should be performed 2–3 days after egg retrieval. Luteal support should be done with vaginal progesterone 200 mg/d till a positive pregnancy test.
Case Study
This is a case of IVF in a complete natural cycle. The only medication we used in this protocol is NSAIDs to control ovulation. NSAIDs induce a temporary LUF (luteinized unruptured follicle) syndrome, while LH surge and oocyte maturation occur normally. As the enzyme cyclo-oxygenase and its product prostaglandin play an important role in the process of follicle rupture, their inhibition by NSAIDs delays ovulation (Nargund et al. 2001). Using this protocol, transvaginal ultrasound controls for follicle monitoring are not necessary any more. The patient detects her LH peak using commercial urinary ovulation indicators at home. Only when urinary LH is positive, the patient needs one hormonal essay of LH and serum estradiol, in order to schedule the exact time point for egg retrieval.
This protocol is very cheap and convenient for the patient. Only one blood test is necessary per cycle, which can be done in any medical laboratory at the patient’s hometown. No vaginal ultrasound has to be done for follicle monitoring. For egg retrieval and embryo transfer, the patient travels to the clinic. The problem with this protocol is that the date and time of LH surge and egg retrieval cannot be influenced. Although it is possible to delay the egg retrieval for 1 day with the use of a GnRH antagonist, the patient has to be available for the procedure at a certain day. The second inconvenience is that statistically, only every second egg retrieval leads to an embryo transfer. As in nearly all of the cases single-embryo transfer is performed, the patient can expect a pregnancy rate of about 30 % per transfer.
A 35-year-old nulliparous woman with 3 years of infertility was referred to our center for IVF. She had undergone an infertility work-up after attempting to conceive naturally for 1 year. She had a normal hormonal profile and normal hysterosalpingogram, and mild endometriosis was found and treated at laparoscopy. Her husband’s semen analysis was normal. They had failed six cycles of gonadotropins–intrauterine insemination (IUI).
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