Megan Freebury Karnis

Fertility, pregnancy, and medical management of Turner syndrome in the reproductive years

Turner syndrome results in infertility in most cases. Fertility preservation through the cryopreservation of oocytes or ovarian tissue may be an option for some girls with Turner syndrome. Oocyte donation results in high pregnancy rates (PR). Those women who plan to pursue pregnancy need comprehensive screening and counseling before and after conception. Pregnancies conceived with either autologous or donated oocytes are at high risk of maternal death from aortic dissection/rupture and are at high risk of serious hypertensive disorders. Reproductive age women with Turner syndrome require ongoing screening for associated medical conditions unrelated to reproduction.

Catastrophic consequences of assisted reproduction: the case of Turner syndrome.

Women with Turner syndrome are generally infertile due to premature ovarian failure. Few may achieve a spontaneous pregnancy, and others may conceive through assisted reproductive technologies including oocyte donation. These pregnancies are high risk due to the medical conditions associated with Turner syndrome. Maternal death from aortic dissection in pregnancies of women with Turner syndrome is estimated at 2%. These pregnancies are also complicated by severe hypertensive disorders and fetal morbidity and mortality. Guidelines for preconception screening and counseling now exist that may mitigate the maternal and fetal risks associated with pregnancy in women with Turner syndrome.

Fertility Preservation for Young Women with Cancer: Hope for the Future

Advances in the diagnosis and successful treatment of childhood, adolescent, and adult cancers have allowed many young women to lead healthy lives after overcoming their disease. However, life-saving cancer treatment often impairs fertility. Chemotherapy and/or radiation may irreversibly damage the reproductive system. The maturing field of assisted conception, and specifically cryopreservation, has created a unique partnership between oncologists and fertility specialists. Improving assisted conception success and fertility sparing strategies provide options for young women who would like to have children of their own after cancer treatment. This review article focuses on the current practices and developing opportunities for women who wish to preserve their fertility when faced with gonadotoxic cancer treatment.

Proposal for a national registry to monitor women with Turner syndrome seeking assisted reproductive technology

Many women with Turner syndrome (TS) are eager to become pregnant. A small number (5%–10%) will have a spontaneous pregnancy, an outcome thought to be more likely in women with mosaicism (1). The increased availability of oocyte donation (OD) through assisted reproductive technology (ART) has enabled an unknown number of women with TS to achieve a pregnancy. A gathering body of evidence, however, suggests that pregnancy is high risk, secondary to potential aortic dissection and rupture and a significant risk of developing hypertensive disorders of pregnancy. The maternal mortality rate is estimated to be approximately 2%, 100-fold greater than all-cause mortality during pregnancy in the general population (1). In one study there was an unusually low prevalence of congenital heart defects (bicuspid aortic valve occurred in 0.8% vs. an expected 25%–50% occurrence), and there were no maternal deaths among 124 pregnancies. However there were potentially life-threatening complications among 3.5% of these pregnancies (2). Clinicians who counsel women with TS currently rely on anecdotal experience, consensus group opinions from national societies, case reports and series, and data obtained by the laborious process of cross-linkage from different national health registries in various Nordic countries (1–4). Although these data are the best available, they are imperfect because of the methodology of ascertainment and the variable inclusion of women with TS who may or may not have been screened for risk factors for aortic dissection and rupture. The 2012 American Society for Reproductive Medicine Practice Committee Opinion states that TS itself is a relative contraindication, and that a ‘‘cardiac MRI revealing any significant abnormality and/or aorta size index (ASI) >2 cm/m represents an absolute contraindication’’ for attempting pregnancy (4). However, the definition of ‘‘significant’’ abnormality is currently not completely understood. It is clear that aortic dilation, the presence or prior repair of coarctation of the aorta, and bicuspid aortic valve are risk factors for dissection and rupture in TS, but unaddressed are the risks associated with rapid changes in aortic dimensions during pregnancy and the significance of elongation of the transverse aortic arch, partial anomalous pulmonary venous connection, pseudocoarctation, persistent left superior vena cava, and aberrant subclavian artery. When recognized, the relative risk contribution of these cardiac lesions is usually assessed clinically by consulting cardiologists. There are currently insufficient data available to adequately counsel women with TS desiring pregnancy about appropriate screening, morbidity and mortality from pregnancy, and long-term follow-up needed after pregnancy. In addition, there is often no opportunity to transfer newly pregnant women to obstetricians who are educated regarding these potential risks.

Risk of Death in Pregnancy Achieved Through Oocyte Donation in Patients With Turner Syndrome: A National Survey

UNLABELLED To determine the risk of death in pregnant women with Turner syndrome who were treated with oocyte donation, and to ascertain the prevalence of preconception cardiac screening in these patients. DESIGN Survey and literature review. SETTING Academic infertility center. PARTICIPANT(S) All 258 donor-egg programs in the 1997 Assisted Reproductive Technology Success Rates publication from the Society for Artificial Reproductive Technology were surveyed by fax or telephone. MAIN OUTCOME MEASURE(S) Death in pregnancy conceived through oocyte donation and proportion of patients prescreened with echocardiography. RESULTS One hundred thirty-four (52%) programs reported 146 Turner patients treated, resulting in 101 pregnancies. One patient died from aortic rupture while awaiting treatment; 72 (49.3%) patients were pre- screened with echocardiography. No deaths in pregnancy were reported. A literature review identified four case reports of Turner patients who died during pregnancy in the United States during the same time period. CONCLUSION(S) The maternal risk of death from rupture or dissection of the aorta in pregnancy may be 2% or higher. Patients with Turner syndrome have not been adequately screened with echocardiography before treatment. Specialists who treat patients with Turner syndrome need to be aware of their cardiac risk and its potential exacerbation from the increased cardiac demands of pregnancy.