A 26-year-old woman with a history of cranial radiation and chemotherapy desired pregnancy. Pelvic ultrasound scanning demonstrated a small uterine volume of 7 mL. After 25 weeks of estrogen therapy, her uterine volume increased to 37 mL. The patient had an uncomplicated pregnancy with the use of donor oocytes and delivered a term healthy daughter.
Numerous advances in the treatment of cancer have allowed many young reproductive-age women to survive disease free. Patients who receive radiation or chemotherapy may exhibit decreased uterine volume and endometrial thickness or impaired uterine blood flow. After total body irradiation, uterine volume may be reduced to 40% of normal adult size and can be decreased even after radiotherapy above the diaphragm. The effect of radiation and chemotherapy depends on the amount and relationship to the onset of endogenous estrogen production. Although spontaneous pregnancies occur in these patients, the risk for preterm delivery and low birthweight is increased. When uterine size is calculated as longitudinal diameter × anterioposterior diameter × transverse diameter × 0.5233, normal volume in nulligravid women ranges from 30-60 mL. Previous studies of estrogen therapy to increase uterine volume have shown variable results.
Case Report
A 26-year-old woman with primary infertility and iatrogenic premature ovarian failure requested fertility therapy. She had undergone surgery, cranial radiation, and chemotherapy for a medulloblastoma at the age of 20 years. Regular cycles had occurred since the age of 12 years but had ceased during chemotherapy. Secondary amenorrhea followed the cessation of oral contraceptive pills. Laboratory studies revealed a follicle-stimulation hormone of 56 IU/L and estradiol level of <20 pg/mL (73.4 pmol/L). Pelvic ultrasound scans demonstrated a uterine volume of 7 mL. The patient opted to attempt estrogen-stimulation therapy to increase her uterine volume, rather than using a gestational carrier. She was started on 3 mg of oral estradiol daily ( Table ). After 12 weeks of therapy, 2 mg of vaginal estradiol twice daily were added. After 25 weeks of total therapy, the oral estrogen dose was increased to 4 mg daily.
| Variable | Start | 2 wk | 12 wk | 25 wk | 51 wk |
|---|---|---|---|---|---|
| Estradiol, mg | |||||
| Oral | 3.0 | 3.0 | 3.0 | 4.0 | 4.0 |
| Vaginal a | — | — | 2.0 | 2.0 | 2.0 |
| Uterine volume, mL | 7 | 14 | — | 37 | 30 |
| Endometrial thickness, mm | 2.7 | — | — | 5.4 | 4.8 |
Results
The uterine volume increased to 14 and 37 mL at 12 and 25 weeks, respectively. After 51 weeks of estrogen therapy, the volume plateaued and was 30 mL. Estradiol levels increased to 1314 pg/mL (4822.38 pmol/L). Two days before decidualization of the endometrium with 50 mg of intramuscular progesterone in sesame oil (Freedom Fertility Pharmacy, Byfield, MA) daily, the uterus was perfused with 300 μg of granulocyte colony-stimulating factor (G-CSF; Amgen Inc, Thousand Oaks, CA). With donated oocytes and her partner’s sperm, 25 embryos were created by insemination. One blastocyst was transferred. She experienced an uncomplicated pregnancy that ended in a spontaneous vaginal delivery of a healthy term daughter who weighed 3175 g.
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