Reduced pregnancy and live birth rates after in vitro fertilization in women with previous Caesarean section: a retrospective cohort study

Abstract

STUDY QUESTION Does a previous Caesarean section affect reproductive outcomes, including live birth, in women after IVF or ICSI? SUMMARY ANSWER A previous Caesarean section impairs live birth rates after IVF or ICSI compared to a previous vaginal delivery. WHAT IS KNOWN ALREADY Rates of Caesarean sections are rising worldwide. Late sequelae of a Caesarean section related to a niche (Caesarean scar defect) include gynaecological symptoms and obstetric complications. A systematic review reported a lower pregnancy rate after a previous Caesarean section (RR 0.91 CI 0.87–0.95) compared to a previous vaginal delivery. So far, studies have been unable to causally differentiate between problems with fertilisation, and the transportation or implantation of an embryo. Studying an IVF population allows us to identify the effect of a previous Caesarean section on the implantation of embryos in relation to a previous vaginal delivery. STUDY DESIGN, SIZE, DURATION We retrospectively studied the live birth rate in women who had an IVF or ICSI treatment at the IVF Centre, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands, between 2006 and 2016 with one previous delivery. In total, 1317 women were included, of whom 334 had a previous caesarean section and 983 had previously delivered vaginally. PARTICIPANTS/MATERIALS, SETTING, METHODS All secondary infertile women, with only one previous delivery either by caesarean section or vaginal delivery, were included. If applicable, only the first fresh embryo transfer was included in the analyses. Patients who did not intend to undergo embryo transfer were excluded. The primary outcome was live birth. Multivariate logistic regression analyses were used with adjustment for possible confounders ((i) age; (ii) pre-pregnancy BMI; (iii) pre-pregnancy smoking; (iv) previous fertility treatment; (v) indication for current fertility treatment: (a) tubal, (b) male factor and (c) endometriosis; (vi) embryo quality; and (vii) endometrial thickness), if applicable. Analysis was by intention to treat (ITT). MAIN RESULTS AND THE ROLE OF CHANCE Baseline characteristics of both groups were comparable. Live birth rates were significantly lower in women with a previous caesarean section than in women with a previous vaginal delivery, 15.9% (51/320) versus 23.3% (219/941) (OR 0.63 95% CI 0.45–0.87) in the ITT analyses. The rates were also lower for ongoing pregnancy (20.1 versus 28.1% (OR 0.64 95% CI 0.48–0.87)), clinical pregnancy (25.7 versus 33.8% (OR 0.68 95% CI 0.52–0.90)) and biochemical test (36.2 versus 45.5% (OR 0.68 95% CI 0.53–0.88)). The per protocol analyses showed the same differences (live birth rate OR 0.66 95% CI 0.47–0.93 and clinical pregnancy rate OR 0.72 95% CI 0.54–0.96). LIMITATIONS, REASONS FOR CAUTION This study is limited by its retrospective design. Furthermore, 56 (16.3%) cases lacked data regarding delivery outcomes, but these were equally distributed between the two groups. WIDER IMPLICATIONS OF THE FINDINGS The lower clinical pregnancy rates per embryo transfer indicate that implantation is hampered after a caesarean section. Its relation with a possible niche (caesarean scar defect) in the uterine caesarean scar needs further study. Our results should be discussed with clinicians and patients who consider an elective caesarean section. STUDY FUNDING/COMPETING INTEREST(S) Not applicable. TRIAL REGISTRATION NUMBER This study has been registered in the Dutch Trial Register (Ref. No. NL7631 http://www.trialregister.nl).

Post-Caesarean section niche-related impaired fertility: hypothetical mechanisms

“…This points to the niche as the causal factor for fluid accumulation. Pregnancy rates were also very promising in that study in which 40.2% of subjects had failed previous IVF therapy; at 2 years of follow-up, 52.0% conceived naturally with a median time to pregnancy of 3.0 months after discontinuation of contraceptives ( Vissers et al , 2020 ). Two other cohort studies on laparoscopic niche repair in 22 and 38 subfertile patients reported high pregnancy rates (55.6% and 44.0%, respectively) in most patients after more than 1-year follow-up ( Tanimura et al , 2015 ; Donnez et al , 2017 ).…”

“…In conclusion, accumulation of fluid is seen in approximately 42% of patients with a large niche ( Vissers et al , 2020 ). This may impair pregnancy outcomes due to reduced implantation yet may also be embryotoxic.…”

“…Live birth rates were lower in women with a previous Caesarean section, at 15.9% versus 23.3% for women with a previous vaginal delivery (odds ratio 0.63 95% CI 0.45–0.87). Of the women in the study, 77% received a single embryo transfer and the quality of embryos did not differ between the two groups ( Vissers et al , 2020 ). The lower clinical pregnancy rate per embryo transfer indicates that implantation is particularly hampered after a Caesarean section.…”

“…Blood in the catheter is one of the criteria for a difficult transfer, which may lead to a lower pregnancy rate ( Tomas et al , 2002 ). Two retrospective studies rated difficulty of embryo transfers in patients with a previous Caesarean section compared with a previous vaginal delivery ( Wang et al , 2017 ; Vissers et al , 2020 ). In the study of Wang et al (2017) , a difficult embryo transfer ratio (9/144 vs. 0/166, P = 0.001) was seen between patients with a history of Caesarean versus only vaginal delivery.…”

“…Various explanations for the cause of post-Caesarean subfertility have been proposed, ranging from placental bed disruption and pelvic adhesions influencing tubal oocyte pick-up ( Murphy et al , 2002 ) to women’s reproductive choices ( Porter et al , 2003 ; Oral and Elter, 2007 ). An increasing variety of therapies to treat niche-related symptoms and improve reproductive outcomes has also been developed and implemented in recent years ( van der Voet et al , 2014b ; Nikkels et al , 2017 ; Vervoort et al , 2018a ; Vissers et al , 2020 ). A recent review including various case series and single-arm cohort studies reported improvement of gynaecological symptoms after (laparoscopic) niche resections.…”