The impact of thyroid autoimmunity on IVF/ICSI outcome: a systematic review and meta-analysis

Study question: Does thyroid autoimmunity (TAI) per sé impact on the outcome
of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)
cycles?
Summary answer: Thyroid autoimmunity seems to have a detrimental impact
on the course of pregnancy achieved through IVF/ICSI but not on the main
outcomes of IVF/ICSI treatment.
What is known already: Thyroid autoimmunity is the most frequent autoimmune
condition and the first cause of thyroid dysfunction among women of reproductive
age. Notably, it has been associated with adverse obstetric outcomes
during all trimesters of pregnancy. Furthermore, since most studies showed an
increased prevalence of TAI among women attending infertility clinics, a detrimental
impact of this condition on natural fertility and on the rate of success of
assisted reproductive techniques (ART) has been suggested. However, to date,
results are inconsistent.
Study design, size, duration: A systematic literature review and meta-analysis
were conducted. A Medline search was performed to identify studies published
from 1990 to 2015 on IVF/ICSI outcome in women with and without TAI. The
primary outcome was delivery rate (DR). Our secondary outcomes were number
of oocytes retrieved (NOR), fertilization rate (FR), implantation rate (IR),
clinical pregnancy rate (CPR) and miscarriage rate (MR). We also extracted
data on age and basal serum concentrations of thyroid stimulating hormone
(TSH).
Participants/materials, setting, methods: Studies were excluded if: (i) only
women with positive TAI were described without a comparison group of
women without TAI, (ii) women were known to have hypothyroidism or hyperthyroidism
or were receiving any treatment for thyroid dysfunction, (iii) serum
TSH was not evaluated before starting the IVF/ICSI cycle, (iv) the participants
were involved with donor oocytes treatment, (vi) each women performed more
than one IVF/ICSI cycle. The study was conducted according to the PRISMA
guidelines.
Main results and the role of chance: We selected 12 studies for the metaanalysis.
Six of the included studies were prospective cohort studies and six
were retrospective cohort studies. Compared with women with negative TAI,
women with positive TAI had a lower DR (OR 0.65; 95% CI [0.49, 0.87];
p = 0.004; 9 studies; 4396 women; I2 = 66%); a higher MR (OR 1.44; 95%
CI [1.06, 1.95]; p = 0.02; 12 studies; 4876 women; I2 = 35%) and a similar
CPR (OR 0.90; 95% CI [0.77, 1.06]; p = 0.22; 12 studies; 4876 women;
I2 = 7%), NOR (SMD 0.10; 95% CI [−0.09, 0.29]; p = 0.28; 5 studies; 1506
women; I2 = 47%), FR (OR 1.11; 95% CI [0.97, 1.27]; p = 0.13; 3 studies; 1082
women; I2 = 0%) and IR (OR 0.98; 95% CI [0.73, 1.32]; p = 0.91; 2 studies;
918 women; I2 = 0%). Both mean age (SMD 0.96; 95% CI [0.66, 1.27]; p <
0.00001; 9 studies; 3256 women; I2 = 85%) and serum TSH (SMD 0.24; 95%
CI [0.15, 0.34]; p < 0.00001; 6 studies; 2098 women; I2 = 59%) resulted higher
in women with TAI.
Limitations, reasons for caution: In the process of systematic review and
meta-analysis the inferences assumed by the data are subject to the limitations
of the primary studies. Furthermore, giving the possible confounding effects
of age and serum TSH, further evidence is warranted prior to draw inferences
on causality.
Wider implications of the findings: Thyroid autoantibodies do not impact on
IVF/ICSI outcome in terms of number of oocytes retrieved and likelihood of
fertilization, implantation and clinical pregnancy. On the contrary, TAI may
have a detrimental effect on the course of pregnancy determining an increased
risk of miscarriage and a decreased chance of delivery.
Trial registration number: Not applicable.