Fertility Issues

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Infertility is strongly associated with endometriosis, and for some it may be the only symptom that they recognize (American Pregnancy Association, 2012). An estimated 30–50% of women with endometriosis have infertility (Macer & Taylor, 2012). Endometriosis can be “minimal” and does not have to be an advanced stage for it to affect fertility (Bloski & Pierson, 2008).

We have collected a few links and articles that address endometriosis and infertility that you can explore and better educate yourself to discuss with your providers. Infertility is a difficult journey that is highly individualized. There is no one correct answer. 

Links/Resources:

Studies:

“The association between endometriosis and infertility is well supported throughout the literature, but a definite cause-effect relationship is still controversial. The prevalence of endometriosis increases dramatically to as high as 25%–50% in women with infertility and 30–50% of women with endometriosis have infertility (2)…. Endometriosis affects gametes and embryos, the fallopian tubes and embryo transport, and the eutopic endometrium; these abnormalities likely all impact fertility. Current treatment options of endometriosis-associated infertility include surgery, superovulation with IUI, and IVF.”

“Endometriosis was associated with a greater risk of pregnancy loss (spontaneous abortion: RR 1.40, 95% CI 1.31–1.49; ectopic pregnancy: RR 1.46, 95% CI 1.19–1.80). Endometriosis was also associated with a greater risk of GDM (RR 1.35, 95% CI 1.11–1.63) and hypertensive disorders of pregnancy (RR 1.30, 95% CI 1.16–1.45).”

“Results showed that the prevalence of high uNK cells was 33.1%. Prednisolone significantly decreased the uNK cell concentration (P < 0.001), however reduction to normal limits was achieved in only 48.3% of patients. There was no difference in any of the pregnancy outcomes or complications between women who had received prednisolone and those who had not. In conclusion, this study showed a relatively high prevalence of raised uNK cells in women with recurrent reproductive failure and confirmed the effect of prednisolone on reducing uNK cell concentrations. We found however no evidence for a significant beneficial effect for prednisolone therapy on pregnancy outcomes. Until the results of an adequately powered RCT become available however, these findings should be considered preliminary.”

“Results. In the study period, 355 women underwent surgery for stage III-IV endometriosis. Follow-up data are available for 253/355 (71%) women. Postoperatively, 142/253 (56%) women attempted to conceive with a conception rate of 104/142 (73%). Confidence intervals for pregnancy for women who were attempting conception (including the nonresponders) range from 104/262 (40%) to 224/262 (85%). Median time to conception was 12 months….Conclusions. These data provide information to women with suspected severe disease preoperatively concerning their likely postoperative fertility outcomes. Ours is a population with severe endometriosis, rather than an infertile population with endometriosis, so caution needs to be applied when applying these data to women with fertility issues alone.”

  • Pantou, A., Simopoulou, M., Sfakianoudis, K., Giannelou, P., Rapani, A., Maziotis, E., … & Koutsilieris, M. (2019). The Role of Laparoscopic Investigation in Enabling Natural Conception and Avoiding in vitro Fertilization Overuse for Infertile Patients of Unidentified Aetiology and Recurrent Implantation Failure Following in vitro Fertilization. Journal of clinical medicine, 8(4), 548. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517944/pdf/jcm-08-00548.pdf 

“In conclusion, laparoscopy appears to be a promising approach, addressing infertility, providing significant diagnostic findings, while avoiding IVF overuse regarding patients of unidentified infertility presenting with recurrent failed IVF attempts.” 

  • Young, K., Kirkman, M., Holton, S., Rowe, H., & Fisher, J. (2018). Fertility experiences in women reporting endometriosis: findings from the understanding fertility management in contemporary Australia survey. The European Journal of Contraception & Reproductive Health Care, 23(6), 434-440. Retrieved from https://pubmed.ncbi.nlm.nih.gov/30481080/ 

“Results: While individual contraceptive use did not differ by endometriosis status, avoiding pregnancy was less important to women reporting endometriosis (50.5%) than to others (68.7%; p < .001). Women reporting endometriosis were approximately three times more likely to report an infertility diagnosis-the majority (39.7%) of which were ‘unexplained female or male infertility’-(p < .001) and six times more likely to report taking longer than 12 months to conceive than those who did not report endometriosis (p < .001). Although more women reporting a diagnosis of endometriosis also reported never having been pregnant (11.9%) than those who did not report a diagnosis (6.0%), this difference was not statistically significant (p = .060). There were also no endometriosis-associated differences in women’s reports of unintended pregnancy, abortion, having been pregnant, or having had a live birth. Conclusions: Our findings counter the common assertion that women with endometriosis are unlikely to conceive, and support the need for health care and information that addresses all aspects of fertility management (not just infertility) for women with endometriosis.”

“Treatment of endometriosis may prevent a number of associated complications of pregnancy, as discussed by Zullo et al. There are numerous theories regarding the pathophysiology of adverse pregnancy outcomes associated with endometriosis. They may be due to a proinflammatory environment with high levels of cytokine production as well as changes to the inner myometrium referred to as the “junctional zone.” Complications include preterm birth, placenta previa, small for gestational age, cesarean section, and miscarriage (1). Other rarer complications of endometriosis in pregnancy also have been described: spontaneous hemoperitoneum in pregnancy, obstetrical hemorrhage, bowel perforation, and appendiceal rupture. Although many endometriomas regress during pregnancy owing to progestational effects, there have been cases of endometrioma rupture and abscess formation. These complications are associated with significant maternal and fetal morbidity and potential mortality. It is not known if endometriosis is the cause of these complications or merely a marker of an independent risk factor, and no studies have evaluated if antepartum treatment of endometriosis or endometrioma improves pregnancy outcomes. One study showed that subfertile women who conceived spontaneously were also at increased risk of pregnancy complications, such as antepartum hemorrhage, cesarean section, pregnancy-induced hypertension, preeclampsia, and very preterm birth. Further studies are needed to elucidate the true relationship between endometriosis and pregnancy complications.”

  • Dunselman, G. A. J., Vermeulen, N., Becker, C., Calhaz-Jorge, C., D’Hooghe, T., De Bie, B., … & Prentice, A. (2014). ESHRE guideline: management of women with endometriosis. Human reproduction, 29(3), 400-412. Retrieved from https://academic.oup.com/humrep/article/29/3/400/707776 

“Are hormonal therapies effective for infertility associated with endometriosis?

Suppression of ovarian function (by means of hormonal contraceptives, progestagens, GnRH analogues or danazol) to improve fertility in minimal to mild endometriosis is not effective and should not be offered for this indication alone. The published evidence does not comment on more severe disease (Hughes et al., 2007).

Is surgery effective for infertility associated with endometriosis?

In women with minimal to mild endometriosis, the evidence, summarised in a Cochrane review, shows that operative laparoscopy is more effective than diagnostic laparoscopy in improving ongoing pregnancy rates. The comparative effectiveness of different surgical techniques is less well studied (Nowroozi et al., 1987; Chang et al., 1997; Jacobson et al., 2010). In women with ovarian endometrioma receiving surgery for infertility or pain, excision of endometrioma capsule increases the spontaneous post-operative pregnancy rate when compared with drainage and electrocoagulation of the endometrioma wall (Hart et al., 2008).”

“The incidence of endometriosis is increasing. Particularly during pregnancy and labour, clinicians should be alert to possible endometriosis-associated complications or complications of previous endometriosis treatment, despite a low relative risk. In addition to an increased rate of early miscarriage, complications such as spontaneous bowel perforation, rupture of ovarian cysts, uterine rupture and intraabdominal bleeding from decidualised endometriosis lesions or previous surgery are described in the literature. Unfavourable neonatal outcomes have also been discussed. We report on an irreducible ovarian torsion in the 16th week of pregnancy following extensive endometriosis surgery, and an intraabdominal haemorrhage due to endometriosis of the bowel in the 29th week of pregnancy.”

  • Li, X., Zeng, C., Zhou, Y. F., Yang, H. X., Shang, J., Zhu, S. N., & Xue, Q. (2017). Endometriosis fertility index for predicting pregnancy after endometriosis surgery. Chinese medical journal, 130(16), 1932. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555127/ 

“The EFI staging system is a 10-point scale system, which considers historical factors, age and length of infertility, and surgical factors, such as the least function score and the AFS score.[5] The second aim of this study was to identify the most significant influencing factor in the EFI system. To date, in women suffering from endometriosis-related infertility, it is difficult to decide when to perform surgical excision and/or fertility treatment. Barri et al.’s study[6] indicated that the highest PRs for women with endometriosis-related infertility are often achieved using a combination of surgery and assisted reproductive technology (ART). The method of combined surgery and ART can provide significantly higher PRs compared with using either of the two treatments alone.[6] Cook and Adamson[7] claimed that it is preferable to perform surgery first, if clinically indicated, and to perform ART if spontaneous pregnancy does not occur after 9–15 months. In 2010, a study[8] by Dominique also suggested that if couples could not conceive naturally for 6–18 months after surgery, they should undergo in vitro fertilization and embryo transfer (IVF-ET). The frequent use of IVF after failure to conceive addresses the issue on the most appropriate individual therapeutic strategy, particularly for couples whose fertility prognosis is radically different. On this basis, the final aim was to investigate the optimal time for IVF-ET after endometriosis surgery. Conclusions: The EFI is a reliable staging system to predict the spontaneous PR of patients. The least function score was the most influential factor to predict the spontaneous PR. Patients with an EFI score ≥5 after 12 months from surgery are recommended to receive IVF-ET to achieve a higher PR.”

  • Barra, F., Mikhail, E., Villegas-Echeverri, J. D., & Ferrero, S. (2020). Infertility in patients with bowel endometriosis. Best Practice & Research Clinical Obstetrics & Gynaecology. https://doi.org/10.1016/j.bpobgyn.2020.05.007 

“Conclusion: In the current literature, the spontaneous fertility of women affected by colorectal endometriosis has been investigated in a few studies [21]. However, it is difficult to clearly define how intestinal endometriosis impacts per se on infertility as this is often associated with other DE lesions involving the uterosacral ligaments, torus uterine, parametrium, vagina or with endometriomas. Besides, patients with colorectal endometriosis may also be affected by focal or diffuse adenomyosis that can also negatively impact per se fertility outcomes. Lastly, multiple other factors (such as age, ovarian reserve, and tubal patency) may influence postoperative fertility outcomes.”

References

American Pregnancy Association. (2012). Endometriosis. Retrieved from https://americanpregnancy.org/womens-health/endometriosis-70984/

Bloski, T., & Pierson, R. (2008). Endometriosis and chronic pelvic pain: unraveling the mystery behind this complex condition. Nursing for women’s health, 12(5), 382-395. doi: 10.1111/j.1751-486X.2008.00362.x