Endometriosis and infertility: a poorly understood association

Published 17 February 2020

Despite its high prevalence and devastating personal consequences, endometriosis remains far from clearly understood, and especially its effects on implantation and pregnancy.

Despite the association of endometriosis with infertility, the exact reasons why this complex and often painful disease affects conception, pregnancy and neonatal outcomes remain an enigma. A well-attended Campus meeting in January, organised by the SIG Endometriosis and Endometrial Disorders, attempted to shed new light on this hot topic based on epidemiological, pathological and clinical findings. It was clear, however, from many presentations that there is a considerable way to go before firm conclusions can be reached.

Kathleen King, from the Endometriosis Association of Ireland, painted a bleak picture of the physical, psychological, social and financial burden faced by many women who can wait years for a diagnosis and then endure multiple surgeries. In her keynote lecture, the medical scientist described how many patients are forced to choose at a young age between continuing their education or trying for a family. The consequences of not achieving motherhood can be considerable. ‘Women can be rushed into fertility treatment which is costly,’ said King, who herself has endometriosis. ‘If this is unsuccessful, they face relationship break-up, guilt and trauma.’

ESHRE’s efforts in producing evidence-based guidelines were praised by King. But more are needed, she said, to reduce diagnosis delays and to address myths around the disease - such as the belief that pregnancy cures endometriosis. Patients should only be referred for therapies which demonstrate clear benefit, and more research into the disease aetiology is crucial in order to develop effective treatments.

All speakers at this Campus highlighted the paucity of research and data, especially around the impact of different types and stages (especially severe) of the disease on fertility.

Ying Cheong, from the University of Southampton in the UK, presented findings from epidemiological studies which suggest a reasonably strong link between the disease and infertility, and indicate endometriosis may lower conception and live birth rates if left untreated. However, only up to one-third of women with endometriosis are estimated to suffer from infertility, which means that most women with endometriosis will actually conceive successfully. Overall, she said, the available evidence is population dependent and subject to selection bias, which makes it impossible to say with certainty that endometriosis causes infertility.

The main obstacles to motherhood for endometriosis patients are impaired implantation and cysts (endometrioma). Failure of embryos to embed can be explained by the fact the disease promotes progesterone resistance (chronic inflammation, defective decidualisation, oestrogen dominance). Yet how or when this develops is unclear, as highlighted by Velja Mijatovic, from UMC Amsterdam. Studies have shown poor implantation rates for IVF/ICSI patients having embryo transfer, but this is based on observational data only. What has also not been established is how disease severity or previous surgery affects implantation success for women having IVF treatment. Learning from donor oocyte programmes, said Mijatovic, suggests implantation is impaired in ovarian failure recipients with endometriosis who are not treated with GnRH agonists.

Controversy continues to surround the damaging effect of endometrioma surgery on ovarian reserve and infertility. The literature widely reports that removal of cysts damages healthy tissue and causes other problems (inflammation, decline in serum AMH levels and in ovarian reserve). Describing the toxic impact of cysts on surrounding tissue, Massimo Candiani from Italy suggested that damage may actually precede surgery. His take-home message was live birth and pregnancy rates after surgery are unaffected by the disease, although the number of oocytes retrieved for ART is diminished, and that experienced surgeons are needed to ensure minimal damage to the ovary.

A widely held theory in endometriosis is that the problem of infertility lies with the egg, and a compelling presentation by Antonio Pellicer, founder of IVI in Spain and an editor of Fertility and Sterility, strengthened the theory that endometriosis can diminish oocyte and embryo quality (through, for example, altered morphokinetics). He said: ‘All papers point to the fact oocytes are different in women with endometriosis.’ An observational study described by Pellicer and currently awaiting publication shows that age (and surgery) are determining factors, with outcomes (oocyte retrieved and pregnancy rate) poorer for women having oocyte vitrification who are aged over 35 and have had surgery.

What about the impact of endometriosis on obstetric and neonatal outcomes? Traditionally, pregnancy is regarded as having a positive effect on the disease. But this view is changing. Reporting his own systematic review , Umberto Leone Roberti Maggiore listed the main triggers for complications during pregnancy in pre-existing endometriosis as adhesions, chronic inflammation and decidualisation). He explained that these (uterine rupture, bowel perforation, etc) are life-threatening but rare.(1) A further systematic review and meta-analysis suggests women could be at increased risk of adverse obstetric outcomes (placenta previa, preterm birth etc) but results were limited by the quality of the studies that were included.(2)

1. Maggiore U, Ferrero S, Mangili G, et al. A Systematic Review on Endometriosis During Pregnancy: Diagnosis, Misdiagnosis, Complications and Outcomes. Hum Reprod Update 2016; 22: 70-103.

2. Lalani S, Choudhry AJ, Firth B, et al. Endometriosis and adverse maternal, fetal and neonatal outcomes: A systematic review and meta-analysis. Hum Reprod 2018; 33: 853-865.

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