IVF/ICSI in a woman with active acromegaly: Successful outcome following treatment with pegvisomant

Abstract

A 29 year old woman with difficult to control acromegaly and a pituitary macroadenoma responded to pegvisomant therapy and subsequently conceived with her first cycle of in-vitro fertilization and intra-cytoplasmic sperm injection. Pregnancy was complicated by gestational diabetes, pituitary gland enlargement and deteriorating visual fields. Conservative management with elective cesarean section was performed at 32 weeks gestation. A healthy boy was delivered who remains developmentally normal at 1 year. This complex case required intricate care by a multidisciplinary team and is likely to represent the first in many cases of assisted conception on pegvisomant therapy for active acromegaly. Keywords Case reportA 29 year old Caucasian woman was diagnosed with acromegaly following a two year history of secondary amenorrhea, change in physical appearance and sweating. The diagnosis was confirmed with an oral glucose tolerance test and radiological imaging that demonstrated a 2.2 cm pituitary tumor compressing the optic chiasm. A bi-temporal visual field defect was confirmed using binocular Goldman perimetry.Over a four-year period, she underwent four transphenoidal hypophysectomies and received 53 Gy radiotherapy. Despite a reduction in tumor size (Fig. 1) and the use of somatostatin analogues, she failed to achieve biochemical cure and her insulin-like growth factor-I (IGF-I) level remained persistently high (96-120 nmol/L; normal range 16-52 nmol/L). Hydrocortisone and thyroxine replacement was required for pituitary deficiency.She was desperate to conceive and was counseled on the effect of pregnancy on acromegaly and the risks of pituitary tumor enlargement. After failing to conceive with clomifene therapy she was referred to the assisted conception unit. Her husband was discovered to be oligoasthenozoospermic and they were counseled for in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).To achieve control of her acromegaly, she was started on daily subcutaneous injections of 20 mg pegvisomant, a highly selective growth hormone receptor (GHR) antagonist, and octreotide was discontinued. Her IGF-I subsequently normalized for the first time in 5 years.Pituitary down regulation was achieved with a GnRH analogue and she required four days of 300 IU recombinant FSH which was increased to 450 IU on day five of stimulation for a further 11 days for super-ovulation. She produced a total of 14 follicles and transvaginal ultrasound-guided oocyte Springer

MANAGEMENT OF ENDOCRINE DISEASE: Acromegaly and pregnancy: a contemporary review

“…Transient (4,91) and total (92) exposure to pegvisomant during pregnancy has been reported. One patient who used pegvisomant throughout pregnancy delivered a healthy and normal-sized baby (92).…”

Acromegaly and pregnancy: a prospective study

“…With the widespread use of pharmacological treatment to control disease activity, a consensus on acromegaly management has recently stated the need to encourage reporting of outcomes in medically treated pregnant patients (13). During pregnancy, pharmacological treatment with somatostatin analogs has been associated with decreased length in newborns (14), whereas cabergoline has been considered probably safe in prolactinomas (15), and pegvisomant, a GH receptor antagonist, has been reportedly used in only two cases (16,17). Although cessation of medical therapy during pregnancy has been usually advised (13), this recommendation results primarily from the lack of a large database on drug safety and not from prospective studies on pregnancy outcomes following drug withdrawal.…”

Pregnancy and pituitary disorders

“…Six patients had recurrence shortly after parturition, and two of them were managed with octreotide and radiotherapy, three of them with octreotide, and one with cabergoline only (108,131). Pituitary imaging studies performed after parturition did not reveal any tumor growth (128,132,133).…”

“…Maternal IGF1 was controlled well, and transplacental passage of the drug was absent or minimal. So the effect on the fetal GH axis is unlikely, and there is no evidence of substantial secretion into breast milk (127,128).…”