Gynecologic and reproductive outcomes in fibrous dysplasia/McCune-Albright syndrome

Abstract

Background Autonomous ovarian activation with recurrent estrogen-producing cysts is a hallmark feature of the rare bone and endocrine disorder fibrous dysplasia/McCune-Albright syndrome. Precocious puberty in girls with McCune-Albright syndrome has been well-described, however long-term effects on gynecologic and reproductive function are unknown. Concerningly, case reports have described poor skeletal outcomes associated with pregnancy in women with fibrous dysplasia. Methods Thirty-nine women with fibrous dysplasia/McCune-Albright syndrome were evaluated as part of a natural history study. Clinical, radiographic, and biochemical data were reviewed. Women were contacted to obtain detailed menstrual and reproductive histories. Results Abnormal uterine bleeding affected 77% of women (30/39), and was associated with severe anemia requiring blood transfusion in 3 cases. Nine women underwent hysterectomy for management of bleeding, including 67% (6/9) at the unusually young age of less than age 35 years. Infertility affected 43% of women (9/21), including 2 women who developed primary ovarian insufficiency after undergoing surgical treatment of ovarian cysts. Of 25 spontaneous pregnancies in 14 women, 35% (8) were unplanned. Among the 14 pregnancies, pregnancy was associated with no change in bone pain in 7 subjects (53%), increased bone pain in 4 subjects (31%), and decreased bone pain in 2 subjects (15%). No additional skeletal complications were reported during pregnancies. Conclusions Women with fibrous dysplasia/McCune-Albright syndrome report a high prevalence of gynecologic morbidity and reduced fertility. There is no clear association between pregnancy and poor skeletal outcomes in this population.

The Clinical Spectrum of McCune-Albright Syndrome and Its Management

“…Between episodes, girls are often clinically asymptomatic with unde-tectable estradiol levels and normal ultrasonographic findings, which may lead to delayed diagnoses. Ovarian torsion is an uncommon complication [25]. Autonomous ovarian activity persists into adulthood and is commonly associated with menometorrhagia and fertility effects [25].…”

“…Ovarian torsion is an uncommon complication [25]. Autonomous ovarian activity persists into adulthood and is commonly associated with menometorrhagia and fertility effects [25].…”

“…Children may require GnRH agonists therapy in addition to these blocking agents for treatment of secondary central precocious puberty [26, 51]. Management of menometorrhagia may include use of progestin-containing intrauterine devices or oral contraceptive pills [25]. Pregnancy is likely achievable and safe in women with MAS; however, ovarian disease may make conception more challenging, and clinicians should have a low threshold to refer patients desiring pregnancy to fertility specialists [25].…”

Auxological and Endocrinological Features in Children With McCune Albright Syndrome: A Review

“…About the course of MAS in female during adolescence and young adult life, persistence of ovarian autonomy, due to estrogen hypersecretion, has been demonstrated. Significant effects on gynecologic function with abnormal uterine bleeding and on reproduction with an increased infertility prevalence have been reported (61)(62)(63).…”

Treatment of primary infertility in McCune-Albright syndrome: a case report of a successful in vitro fertilization cycle

“…Since then, the literature focuses mainly on the treatment of precocious puberty in children with MAS. In adulthood, other gynecologic issues such as infertility play a larger role, but there is limited understanding regarding the management of infertility in MAS patients despite the high prevalence of infertility in this population (5). Four other case reports have been conducted to evaluate the management of infertility in MAS, all of which demonstrated that unilateral oophorectomy resulted in the return of ovulatory function and pregnancy.…”