Aspirin, NSAIDS & Infertility

Doctors may not mention this to women who are trying to get pregnant, but the use of non-steroidal anti-inflammatory drugs, including Advil and Aleve, and aspirin cause ovulation problems. Specifically, the use of these medications can cause a failure of the follicles to burst and release eggs — called luteinizing unruptured follicle syndrome(LUF or LUFS). Below are some abstracts on the subject. Full journal articles may be ordered through Medline or found at medical libraries. I’ve included the link and here is the url as well: http://www.fertilityplus.org/faq/nsaids.htmlfor you to go right to the source. NSAIDS,Aspirin & Infertility – Journal Abstracts

Citation: Smith G, Roberts R, Hall C, Nuki G, Reversibleovulatory failure associated with the development of luteinized unruptured follicles in women with inflammatory arthritis taking non-steroidal anti-inflammatory drugs., Br JRheumatol 35: 5, 458-62, May, 1996. Address: Rheumatic Diseases Unit Western GeneralHospital Edinburgh.


The case histories of three young women with ankylosing spondylitis, rheumatoid arthritis and a seronegative inflammatory polyarthritis undergoing investigations for infertility are presented. In each, non-steroidal anti-inflammatory drug (NSAID) therapy was associated with the recurrent development of luteinized unruptured ovarian follicles and normal ovulation following drug withdrawal. It is suggested that NSAID therapy may be an important and frequently overlooked cause of anovulation and infertility.

Citation: Akil M, Amos RS, Stewart P, Infertility may sometimes be associated with NSAID consumption., Br J Rheumatol 35: 1, 76-8, Jan, 1996. Address: Department of Rheumatology Leicester Royal Infirmary UK.


Non-steroidal anti-inflammatory drugs are widely used in the treatment of inflammatory joint diseases. Many patients suffering from these disorders are young women during their childbearing years. We report three cases of infertility where the cause may have been NSAID-induced ‘luteinized unruptured follicle’ syndrome. This phenomenon is well recognized in obstetric circles, and we would like to bring it to the attention of rheumatologists since it is not documented in the rheumatological literature.

Zanagnolo V, Dharmarajan AM, Endo K, Wallach EE, Effects of acetylsalicylic acid (aspirin) and naproxen sodium (naproxen) on ovulation, prostaglandin, and progesterone production in the rabbit., Fertil Steril 65: 5, 1036-43, May, 1996. Address: Department of Gynecology and Obstetrics Johns Hopkins University School of Medicine Baltimore Maryland USA.


OBJECTIVE: To determine the effects of acetylsalicylic acid (aspirin) and naproxen sodium (naproxen) on ovulation, ovarian prostaglandins (PG), and P production in the rabbit via in vivo and in vitro studies.

DESIGN: Aspirin and naproxen were administered i.v. 6.5 and 7 hours, respectively, after hCG administration to New Zealand White adult female rabbits. Laparotomy was performed 24 hours after hCG administration. For in vitro experiments, control animals underwent laparotomy 6.5 (aspirin) and 7 hours (naproxen) after hCG administration. The treated animal received aspirin and naproxen; laparotomy was performed 1 hour later. One ovary was perfused for 6 hours with aspirin or naproxen whereas the contralateral ovary served as a control and was perfused with control medium (M199; GIBCO, Grand Island, New York). Perfusate samples were collected at 1-hour intervals for PG and P determination. SETTING: A conventional laboratory setting. INTERVENTIONS: In vivo experiments used i.v. administration of 100 mg/kg aspirin and 10 and 50 mg/kg naproxen. In vitro perfusion was also carried out with 100 micrograms/mL aspirin and 10 and 50 micrograms/mL naproxen added to the perfusate. MAIN OUTCOME MEASURES: Ovulatory efficiency (no. of ovulations/no mature follicles) and ovarian vein PG and P concentration were determined.

RESULTS: Ovulatory efficiency was 88% for control, 41% for in vivo aspirin-treated, and 40% (10 mg/kg) and 0% (50 mg/kg) for naproxen-treated rabbits. Aspirin and naproxen were associated with decreased ovulatory efficiency when administered in vitro to both in vivo control and in vivo treated ovaries (control-medium = 70%; control-aspirin = 14%; aspirin-medium = 34%; aspirin-aspirin = 0%; control-naproxen = 25%; naproxen-medium = 38%; naproxen = 0% with 10 microgram/mL, and control-naproxen = 13%; naproxen-medium = 0%; naproxen = 0% with 50 micrograms/mL). Prostaglandin F2 alpha was undetectable in the perfusate of those ovaries perfused of those ovaries perfused either with aspirin or naproxen. Ovarian venous concentration of P in the perfusate was similar in all groups.

CONCLUSIONS: Aspirin and naproxen significantly reduced ovulatory efficiency and PG production both in vivo and in vitro in hCG-treated rabbits. A critical period of 6.5 and 7 hours after hCG administration was established.

Espey LL. Kohda H. Mori T. Okamura H. Rat ovarian prostaglandin levels and ovulation as indicators of the strength of non-steroidal anti-inflammatory drugs., Source Prostaglandins. 36(6):875-9, 1988 Dec. Address: Institution Biology Department, Trinity University, San Antonio, Texas 78284.


Immature Wistar rats were treated with pregnant mare’s serum gonadotropin and human chorionic gonadotropin to induce ovulation. The non-steroidal anti-inflammatory drugs indomethacin, diclofenac, flurbiprofen, and phenylbutazone inhibited both the ovulation rate and the normal increase in ovarian prostaglandin E during ovulation. Tolmetin, ibuprofen, and aspirin did not have any significant effect. There was a significant correlation between the ovulation rate and the level of ovarian prostaglandin E following treatment with these drugs. When indomethacin was given in graded doses, there was also a correlation between ovulation rate and the dose-dependent inhibition of ovarian prostaglandin E.

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