Levothyroxine and treatment of other thyroid disorders
Thyroid disease is associated with ovulatory dysfunction, reduced rates
of conception, miscarriage and adverse pregnancy and early neonatal
outcomes (33). Hypothyroidism is a disease which prevalence increases,
particularly in women, as they get older (34). As with the older average
age of women undergoing ART, there are more patients likely to be on
levothyroxine therefore it is important to establish the safety of this
drug. One retrospective study analysed reproductive outcomes of
euthyroid women compared to women with hypothyroidism on levothyroxine
undergoing ART and found that despite the treated group having
significantly lower implantation rates, both groups had similar
pregnancy rates and miscarriage rates, irrespective of age (35).
Recently, guidelines have been updated as evidence suggests that even
subclinical hypothyroidism, where patients are asymptomatic and bloods
tests are borderline, should be treated in order to improve reproductive
outcomes for patients undergoing ART (33, 36). Chung-Hoon K et al.
performed a prospective randomised control trial involving 64 patients
and found that levothyroxine treatment can improve embryo quality and
pregnancy outcome in subclinical hypothyroid women undergoing ART
compared to those who received placebo (37).
Pelliccione F et al. performed a retrospective study on the outcomes of
levothyroxine-supplemented women with subclinical hypothyroidism. They
analysed 6545 cycles from 4147 women and found that there was no
discernible difference between implantation or pregnancy rates between
the treated and untreated women. The study did note that the benefit of
levothyroxine was that it mitigated the negative effects on the thyroid
axis from controlled ovarian stimulation (38).
However, a double-blinded placebo controlled multicentre trial which
randomised 19585 euthyroid women with positive thyroid peroxidase
antibodies and history of previous miscarriage or infertility to 50 mcg
thyroxine or placebo noted no significant difference in the live birth
rate or other pregnancy and neonatal outcomes (39). Patients with
clinical or subclinical hypothyroidism should have thyroid stimulating
hormone levels maintained at less than 2.5mU/L pre-conception (which is
lower than the normal range, 0.4 to 4 mU/L, for non-pregnant women) and
throughout pregnancy to optimise reproductive outcomes (40).
Hyperthyroidism is thought to affect 2.3% of women presenting with
subfertility compared to 1.5% of the general population (33). Most of
these women present with oligomenorrhoea or polymenorrhoea and the
impact of treatment of hyperthyroidism prior to and during ART is yet to
be assessed. Commonly radioiodine treatment is used in these patients
and no adverse effect on gonadal function or neonatal outcomes have been
noted as long as radioiodine treatment has occurred at least 6 months
prior to pregnancy. Thyroid dysfunction occurs less commonly in males
compared to females however has been linked to male factor infertility.
Further research is required on the treatment of thyroid disease in male
partners and ART outcomes (41).