Reproductive outcomes in pregnant women aged 35 or older: the role of individual repair capacity

Abstract

Abbreviations: 8-OH-dG -8-hydroxydeoxyguanosine, AMA -advanced maternal age, AR -assisted reproduction, BER -base excision repair, CDC -US Centre for disease prevention and control, DIC -disseminated intravascular coagulation, DS -Down syndrome, HELLP -haemolysis/elevated liver enzymes/low platelets, ICSI -intracytoplasmic sperm injection, IRC -individual repair capacity, IUGR -intrauterine growth restriction, IUI -intrauterine insemination, IVF -in vitro fertilisation, LIF -leukaemia inhibitory factor, NER -nucleotide excision repair, PCOS -polycystic ovary syndrome, PIH -pregnancy-induced hypertension, ROS -reactive oxygen species, TTD -trichothiodystrophy, w.g. -weeks of gestation, WHO -World Health Organisation, XP -xeroderma pigmentosum. AbstractAt present, childbirth is being progressively postponed until later age. Women aged 35 or older may have to wait longer to conceive than younger women and are more likely to be referred to fertility evaluations, but in a significant proportion a spontaneous conception would be achieved in the timeframe typical of younger women. Pregnancies where mothers are ≥ 35 are associated with more risks for pregnancy loss, chromosomal disease, pregnancy-associated complications, prematurity and low birthweight. These concerns, however, are not uncommon in younger women as well. This puts forward the question whether advanced age per se is the underlying cause for the increased risk for adverse outcomes in older pregnant women, or whether there might be other factors that account for it but do not radically worsen the prospects for favourable outcomes. The individual risks associated with childbirth late in life may stem from maternal genetic background rather than being a simple function of age. There is plenty of preliminary evidence that individual capacity for identification and repair of DNA damage may constitute a major factor in female fertility and fecundity. Subtle deficiencies in the repair capacity may have little to no importance in younger pregnant women but may make a significant difference in older women. The outcomes of pregnancies in women >35 are largely dependent on the prepregnancy health status and the quality of antenatal care, and may not be dramatically different from outcomes in younger women.

Twinning as an Evolved Age-Dependent Physiological Mechanism: Evidence from Large Brazilian Samples

“…Many factors may lead to this increase, such as increasing body mass index in women, improvement of quality of life, increase in social support, postponement of pregnancies until higher ages, use of assisted reproduction technologies and an increase in air pollution [22]. The pattern obtained in São Paulo city is aligned with the pattern in earlier decades in São Paulo [71] and with the worldwide increase in twinning rates (e.g., [42,72,73]), especially over the last several decades [68].…”

“…However, considering the aforementioned risks of having a twin pregnancy, the pregnancies of mothers of higher age (≥35 years old), in general, are already associated with more chromosomal disease, complications, prematurity and low birth weight, and risks for abortion [68]. Thus, the fitness benefits of having twins in higher age must outweigh not only the costs of twinning, but also the costs of later age at conception.…”