Recurrent Pregnancy Loss and Inappropriate Local Immune Response to Sex Hormones

Abstract

Recurrent pregnancy loss may be associated with inappropriate local immune responses to sex hormones. Further research is necessary into the mechanisms of hypersensitivity to estrogen and progesterone and their interactions with other systems.

The autoimmune bases of infertility and pregnancy loss

“…Intolerance to sex steroid hormones is not uncommon and may present in numerous forms including premenstrual syndrome, dysmenorrhea, and mammary pain with a cyclic pattern resembling the menstrual cycle. In some cases, infertility and recurrent miscarriages may manifest in patients with progesterone hypersensitivity [5,6] through enigmatic mechanisms, possibly similar to IgE-associated drug hypersensitivity. The most used therpaeutic approach is based on hormone desensitization, commonly in three steps, resulting in successful IVF [5].…”

“…Similarly, cytokine modulation can also be used acting on Th2 and Th1 molecules, albeit in opposite ways. The possibility of an autoimmune response to steroid hormones presenting with infertility [5] or pregnancy loss [6] should be considered in this scenario.…”

Detection of non‐criteria autoantibodies in women without apparent causes for pregnancy loss

“…12,15,16 Anti-nuclear antibodies (ANA), which is a routine screening test for systemic lupus erythematosus (SLE), were found to be increased in RPL patients according to a review published in 1996. 17 Similarly, anti-sperm antibody (ASA) 7,18 and anti-endometrium (aEM) antibody 7 resulting in implantation failure and endometriosis, respectively, have also been shown to be attributable to infertility. Even with all the endeavors to identify autoantibodies associated with miscarriage, most previous studies did not generate sufficient or consistent results except for conventional aPLs (LA, aCL, and aβ2-GPI).…”

Steroid hormone hypersensitivity: clinical presentation and management

“…We have used a three-step procedure of desensitization to sex hormones until a negative skin test is obtained. This approach has led to sustained improvement of premenstrual phenomenon (5) and live births in a group of women with recurrent miscarriage (manuscript in preparation). Pieto Garcia et al (1) used a rapid desensitization protocol to increasing doses of P administered vaginally.…”

“…However, visual analog scoring is of little use for other maninfestations of hormone hypersensitivity. Because the skin most commonly demonstrates the signs of hormone hypersensitivity, various forms of skin testing have been used (1,5,24). Thosee authors inject a test dose of E 2 and P into the forearm intradermally in the luteal phase of the cycle.…”