INTRODUCTION: Infertility affects 15% of couples. IVF is the most commonly used therapy for infertility. Progesterone is used for luteal phase support during IVF. Sesame oil is the common excipient. Cases of eosinophilic pneumonia have been described after IVF and are likely caused by the sesame oil component of progesterone. None of these cases have bronchoscopic tissue confirmation.
CASE PRESENTATION: 39yr old female, being treated for primary infertility. She had tried clomiphene citrate treatment which was not successful. She underwent ovulation induction with Follistim, Menopur, HCG and ganirilix. IM progesterone was started after egg retreival on November 9, 2010. Last injection of progesterone-in-sesame oil (P-in-sesame oil) was on November 23. She developed shortness of breath and pleuritic chest pain on November 26. Her symptoms worsened on November 29, she went to ED for evaluation. D-dimer was elevated, CT chest revealed bilateral peripheral ground glass infiltrates with interstitial thickening and no pulmonary embolism. She was admitted for further evaluation. She had peripheral eosinophilia with AEC of 1590/μL. She was started on ceftriaxone and azithromycin. She had bronchoscopy and BAL done on 12/1/10, and IV steroids were started the same day for possible eosinophilic pneumonia. Investigations for infectious causes were negative, antibiotics were discontinued. BAL differential cell count showed 75% eosinophils. Transbronhial biopsy showed a pattern of acute lung injury. Interstitial infiltrate comprised of neutrophils, and focally, of eosinophils was present. While the tissue eosinophilia was not diffuse, the focal increase was suggestive of acute eosinophilic pneumonia. IgE level was normal. Patient improved dramatically on steroids and was discharged on 12/3/10. She was asymptomatic with complete clearing of the ground glass infiltrates on 1/6/2011. Skin allergy testing was negative for sesame seed. Subsequent IVF cycles were planned with vaginal progesterone which does not contain sesame oil. Patient achieved pregnancy without further cycles of IVF.
DISCUSSION: The acute eosinophilic pneumonia was likely precipitated by the sesame oil component of im progesterone. Literature search revealed 5 similar cases. In all patients, including ours, the symptoms occurred 2-4weeks after initiation of P-in-sesame oil injections. Patients present with an acute respiratory illness of 2-3-day duration. Most common symptoms are dyspnea, dry cough and fever. Bibasilar rales are the most common exam finding. Chest X-ray reveals alveolar or interstitial infiltrates most prominent in basilar peripheral lung. Complete resolution is expected after P-in-sesame oil is discontinued. Most symptomatic patients were treated with short courses of systemic steroids with clinical and radiographic improvement within days. IgE levels were normal in all reported cases; intradermal test results are variable. Our patient had a negative skin test for sesame seed. Delayed-type hypersensitivity reaction has been presumed to be another mechanism. All reported patients tolerated vaginal P-in-sesame oil or progesterone preparations in peanut or olive oil without any adverse events. Our patient achieved pregnancy without any further cycles of IVF.
CONCLUSIONS: 1. Sesame oil, used as excipient in im progesterone preparation can cause acute eosinophilic pneumonia. 2. Rapid recovery occurs within days after stopping the P-in-sesame oil and short courses of steroid therapy. 3. Alternative treatments of luteal phase support such as vaginal preparations of P-in-sesame oil or progesterone with a different excipient (peanut or olive oil) are subsequently tolerated well. 4.Eosinophilic pneumonia should be included in the differential diagnosis of acute pneumonia-like illness during pregnancies achieved with IVF.
Reference #1 Khan A, Jariwala S, Harry JL. Acute eosinophilic pneumonia with intramuscular progesterone after in vitro fertilization. Fertility and sterility 2007;90:e3-e6.
Reference #2 Bouckaert Y, Robert F, Englert Y. Acute eosinophilic pneumonia associated with intramuscular administration of progesterone as luteal phase support after IVF: Case report. Human reproduction 2004;19:1806-1810
Reference #3 Phy JL, Weiss WT, Weiler CR, et al. Hypersensitivity to progesterone-in-oil after in vitro fertilization and embryo transfer. Fertility and Sterility 2003;80:1272-1275.
DISCLOSURE: The following authors have nothing to disclose: Gaurav Dagar, Nevin Uysal Biggs, Rade Tomic, Arjun Rao
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