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Since the first documentation of the reproductive risk associated with treatment almost a decade ago, more than 50 observational studies have been published confirming or disputing these associations; some of these reporting data from large population-based datasets. Individual attempts to synthetize parts of this rapidly evolving evidence base in small systematic reviews and meta-analyses reached contradictory conclusions and initiated debates and confusion within the scientific community.
Media publicity has heightened public awareness that treatment for cervical precancer is associated with an increased reproductive morbidity. There has been a substantial increase in enquiries from patients and clinicians on the risks associated with different treatment techniques and cone depths, and as to how this risk may be managed and prevented. With a rapidly evolving evidence base and lack of a robust synthesis of the published literature, these questions are becoming increasingly difficult to answer.
We recently conducted a series of systematic reviews and meta-analyses to explore the impact that CIN treatment on reproductive outcomes and to explore how this risk may be modified by the cone depth and comparison group. There was no evidence that fertility was affected after CIN treatment, although the risk of mid-trimester miscarriages was substantially higher. We also found that all local cervical treatments (excisional or ablative) increase the risk of preterm birth and adverse sequelae in a subsequent pregnancy. The magnitude of the effect of treatment was higher for more radical techniques and for excision rather than ablation. Multiple conisations increased four-fold the risk of preterm birth as compared to untreated controls. Subgroup analyses clearly demonstrated that the risk of preterm birth directly correlates to the cone dimensions (depth/volume) and progressively increases with increasing cone depth. Although the risk was increased even for excisions measuring less than 10mm in depth, this was almost two-fold higher for excisions of more than 10mm, three-fold higher for more than 15/17mm and almost five-fold higher for excisions exceeding 20mm in depth. We also found that although women with CIN have a significantly higher baseline risk of prematurity as compared to the general population, cervical treatment and particularly long cones further increase that risk.
The underlying mechanism is unclear; hypotheses include immunomodulation relating to HPV infection affecting parturition pathways, and acquired ‘mechanical weakness’ secondary to loss of cervical tissue. Future research should explore different possible aetiologies.