Uterine environment ‘as important as the embryo’ in affecting implantation and pregnancy

Published 27 October 2020

An online Campus meeting held in October reviewed the diagnosis of uterine abnormalities and the minimally invasive surgical - and emerging medical - approaches in their management ahead of fertility treatment.

Growths, chronic inflammation and other abnormalities affecting the womb such as congenital malformations are all implicated in IVF failure, miscarriage and premature labour. This makes the uterine environment as important as the embryo in determining fertility outcomes.

The speakers at this first Autumn online Campus meeting in October, organised by the SIG Reproductive Surgery, emphasised how diagnosis and treatment of these often chronic conditions have advanced, with minimally invasive techniques to preserve the uterus - such as hysteroscopy - now widely available. But evidence is still lacking of efficacy in improving pregnancy rate, consensus has yet to be reached on the best diagnostic approaches and classification of anomalies is still proving a challenge.

Myomectomy is the most evidence-based approach for fibroid removal, with studies showing a pregnancy rate of up to 68% in patients who otherwise face poor IVF outcomes, possibly as a result of uterine cavity distortion, and poor implantation success. Attila Vereczkey, president of the Hungarian Human Reproduction Society, told the online audience that hysteroscopy is the preferred excision method. High-intensity focused ultrasound and uterine artery embolisation are among experimental management strategies and not yet recommended as front-line treatment. Vereczkey’s take-home message was to follow the rules: get informed consent, map fibroids, plan surgery and explore minimally invasive techniques where possible.

A lack of randomised controlled trial evidence means no gold standard yet exists for adenomyosis – treatment is always case-by-case, especially for cytoreductive techniques. ‘An easy-looking fibroid can be hard, and a difficult one easy,’ was how Antoine Watrelot summed up the situation, highlighting how diagnosis can be challenging despite MRI and ultrasound. A recent review has indicated that pregnancy rates for focal adenomyosis patients appear to be higher after conservative surgery compared with diffuse adenomyosis (53% vs 34%) but more trials are needed to prove benefit.(1)

Bela Molnar discussed the challenges of managing patients with congenital uterine malformations such as bicornate uteri. Once again, hysteroscopy is the treatment of choice based on reproductive results and other factors, but who to treat and how many times remains a dilemma - and the aim of restoring normal uterine architecture is not always possible, said Molnar.

For subfertile women with minor abnormalities or subtle lesions of the endometrial cavity, hysteroscopy appears to be of potential benefit, yet multicentre study evidence is limited because the procedure ‘works with images, and images can be misleading’. So said Stephan Gordts, adding that diagnosis can also be hampered by a lack of uniform terminology to describe these unsuspected intrauterine pathologies which have an hysteroscopy discovery rate of between 25 and 56%.

The picture is similar for hysteroscopy in the assessment of chronic endometritis, which is a significant cause of recurrent miscarriage (9-43%) and repeat failed IVF (14-56%). Although seen as a gamechanger, the diagnostic accuracy of office hysteroscopy using fluid media has varied widely across studies, prompting attempts to reach consensus on the endometrial features of chronic endometritis.(2) Checking for chronic endometritis remains vital, according to Sergio Haimovich, as underlined by his own clinic’s 40% positive rate. As for treatment, a ‘simple’ regime of doxycycline (200 mg daily for 14 days) can decrease abortion and increase implantation rates for chronic endometritis patients, outcomes yet to be corroborated by well-designed prospective studies.

The current thinking is that chronic endometritis may be caused by a variety of reproductive tract microbiota. Evidence presented by Andrea Bernabeu suggests an association between chronic endometritis and significantly higher abundance of 18 bacterial taxa in the endometrial cavity, and that endometrial microbiota affect ART implantation success/failure.

The question is, could an abnormal microbiome be cured? Science does not yet have an answer. Research on antibiotic use is inconclusive, said Bernabeu, and also on probiotics, although the latter do appear to modify the pattern of expression in vaginal microbiota.

1 Tan J, Moriarty S, Taskin O, et al. Reproductive outcomes after fertility-sparing surgery for focal and diffuse adenomyosis: A systematic review. J Minim Invasive Gynaecol 2018; 25; 608-621.
2 Cicinelli E, Vitagliano A, Kumar A, et al. Unified diagnostic criteria for chronic endometritis at fluid hysteroscopy: proposal and reliability evaluation through an international randomized-controlled observer study. Fertil Steril 2019; 112; 162-173.

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