Ultrasound B-mode changes in the uterus and ovaries and Doppler changes in the uterus after total body irradiation and allogeneic bone marrow transplantation in childhood

Abstract

Summary:Internal genitalia and uterine blood flow were assessed by ultrasound in 12 females 4.0-10.9 years after total body irradiation and allogeneic bone marrow transplantation for childhood leukaemia or lymphoma. Median age of the participants was 12.7 years (range 6.1-17.6) at bone marrow transplantation and 21.5 years (11.6-25.6) at the follow-up study. At follow-up all had entered puberty and 11/12 females had experienced the menarche. Eight females received sex steroid replacement therapy, three had spontaneous pubertal development and one woman experienced symptoms of estrogen deficiency. Median uterine and ovarian volumes were significantly reduced to ؊2.6 standard deviation scores (SDS) (؊6.3 to ؊0.6), P ‫؍‬ 0.002, and ؊2.6 SDS (؊4.8 to ؊0.5), P ‫؍‬ 0.002, respectively, compared with normal controls. Follicles were only detectable in two individuals. Uterine blood flow was impaired, as a systolic blood flow could be measured in 6/9 individuals, and a diastolic blood flow in 1/9 females. Our results indicate that the prescribed dosage of hormone replacement therapy, which was sufficient to induce bleeding and suppress other stigmata of premature menopause, was inadequate to generate normal uterine growth. In order to achieve uterine growth higher doses of hormone replacement therapy may be required. Our results confirm pelvic ultrasound as a reliable tool for investigation of internal female genitalia; however, in an infertility setting further tests are indicated. Keywords: BMT; TBI; childhood; uterus; ovary; uterine blood flow During the past two decades allogeneic bone marrow transplantation (BMT) has been used in the treatment of children with relapsed or very high risk leukaemia and lymphoma. Since many of these children become long-term survivors, the late effects of treatment are of major concern. Preparative regimens for BMT, high-dose chemotherapy alone or in combination with total body irradiation (TBI), may cause various endocrine abnormalities, 1-10 and ovarian failure Correspondence: K Holm, Department of Growth and Reproduction, Section 5064, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark Received 26 March 1998; accepted 5 September 1998 resulting in life-long need for sex steroid replacement therapy (HRT) and infertility is common. Recovery of ovarian function occurs especially when preparative regimens do not include TBI, 5-11 and cases of pregnancies resulting in successful deliveries have been reported even when preparative regimens have included TBI. [12][13][14][15][16][17][18][19][20] The progress of assisted reproduction and the availability of oocyte donation has made pregnancy a possibility in women without ovarian function, provided there is normal function of the uterus. However, once pregnancy has been achieved, other problems may occur. In patients treated for solid tumours abdominal irradiation with 20-30 Gy have caused irreversible damage to uterine musculature and blood flow 21 and a high risk of adverse pregnancy outcome, eg low birth weight and increased perinat...

Final height and gonad function after total body irradiation during childhood

“…24 The fibrosis and alterations in the vascularization of the myometrium are additional causes of infertility. 25 The girls given TBI and having spontaneous cycles had smaller median ovary volumes and lower median total follicle numbers evaluated by echography and higher plasma FSH concentrations than those given other treatment for childhood cancer. 26 …”

DIAGNOSIS OF ENDOCRINE DISEASE: Endocrine late-effects of childhood cancer and its treatments

“…Even with spontaneous puberty and/or normal progression of development, premature menopause may still occur. Women having normal menstrual cycles and those able to become pregnant despite a history of exposure to TBI experience high rates of miscarriage that have been attributed to adverse effects on the uterus and/ or its blood supply (130,152,153 I-MIBG for neuroblastoma was also reported to be a risk factor of POI (161). Data on fertility outcomes off-therapy and long-term for novel targeted chemotherapy agents are limited (8, 140).…”

Acute effects of pelvic irradiation on the adult uterus revealed by dynamic contrast-enhanced MRI

“…Ultrasounds of paediatric cancer survivors suggest that pelvic RT alters uterine volume, distensibility and vasculature, with patients who are younger at the time of RT being the most vulnerable to these effects [5][6][7]. Additionally, population-based studies of paediatric cancer survivors have demonstrated an association between abdominal and/or pelvic RT and adverse pregnancy and neonatal outcomes, including placental abnormalities, pre-term delivery, low birth weight infants and perinatal mortality [8][9][10][11].…”