Sharma et al performed a retrospective cohort study of 973 women with adenomyosis, and reported that the clinical pregnancy rate after fresh cleavage stage embryo transfer (day 2/3) in IVF-ICSI cycles was significantly reduced when endometriosis was associated with adenomyosis than endometriosis alone (36.62% vs 22.72%; OR = 1.96, CI = 1.14–3.38). They also found that the groups having adenomyosis with endometriosis had significantly lower clinical pregnancies than those with tubal factor infertility [34.5% (161/466) vs.22.72% (20/88); OR = 1.79, CI = 1.05–3.06], where as those with adenomyosis without endometriosis had comparable pregnancy rate than cases with tubal factor[34.5(161/466 vs. 15/64(23.44%); OR = 1.72, CI = 0.93–3.17]. Though actually the pregnancy rate is lower in Adenomyosis group than tubal factor group, this did not reach statistical significance. This may be due to non-homogeneous distribution of cases where in tubal factor group, which was 6 times larger than Adenomyosis group (466 vs.64)27. Thalluri et al performed a retrospective cohort study of 213 patients with adenomyosis who underwent IVF and fresh (day4/5) embryo transfer. The clinical pregnancy rate in adenomyosis and non-adenomyosis groups were 23.6% and 44.6% (P = 0.017), and miscarriage rates were 25% and 10% (P = 0.144), and biochemical pregnancy rates were 31.6% vs 49.7% (P = 0.042), respectively11. In our study, the pregnancy, clinical pregnancy and live birth rates were significantly reduced in group A compared to group B. Moreover, we had the cases and controls in comparable numbers (47 and 42) and have included women with only tubal factor infertility (without coexisting other infertility factors) as controls.
Ballester et al performed a prospective multicentric cohort study in women with colorectal endometriosis who underwent ICSI-IVF. In this study, 21(28%) of 75 women had adenomyosis. The cumulative pregnancy in three embryo transfers were 19% for those with associated adenomyosis compared to 82.4% for those without adenomyosis. Adenomyosis was found to independently affect pregnancy rates in ICSI, in that study28.In our study, the number of cases with co-existing endometriosis were proportionately lower(14.2%) and hence such a comparison could not be made. Salim et al performed a prospective observational study in 275 women with adenomyosis who underwent IVF-ICSI. The study participants were grouped as normal (n = 256) and-adenomyosis (n = 19). The adenomyosis group had a significantly lower pregnancy rate (47.2% vs 22.2%, P < 0.001), lower implantation rate (29.4 vs 18 hi.8% P < 0.001), and significantly higher miscarriage rate (2.8 vs 50%, P < 0.001). But the groups were extremely heterogeneous in numbers (256 vs 19). Moreover, the normal group contained cases with other infertility factors such as male factor, endometriosis, anovulation, unexplained along with tubal factor rather than tubal factor alone. There is a probability that those results would have been modified by the presence of these factors (effect modifiers)14. But in our study, we included only those women with tubal factor infertility alone as controls, thereby increasing the validity of our results. Our study showed significantly lower pregnancy, implantation and clinical pregnancy rates in women with adenomyosis (Group A). The miscarriage rates in our study were higher in the cases (Group A) but did not reach statistical significance, probably due to lower numbers in the study groups. In a systemic review and meta-analysis performed by Younes et al, adenomyosis was found to significantly reduce the pregnancy rate per embryo transfer (OR = 0.753, CI = 0.610–0.930), in women undergoing IVF-ICSI compared to those without adenomyosis23. These findings were similar to our study.
Benaglia et al performed a prospective case-control study of 98 women (49 vs 49) who underwent IVF-ICSI and fresh embryo transfer (day 2 to day 5). In their study, the clinical pregnancy rate was 29% in adenomyosis group and 43% in controls, which was higher but did not reach statistical significance (OR = 1.88, CI = 0.81–4.34). The implantation rates were 32% and 21% (P = 0.14), and the live birth rates were 35% and 18% (OR = 2.36; CI = 0.93-6.00) that were not statistically significant. In this study though the controls were matched, they consisted of other factors of infertility such as male factor, endometriosis, decreased ovarian reserve and unexplained factor. Matching would reduce the confounding bias but may not eliminate it. In our study we did not include women with infertility factors other than tubal factor in the control group. This discrepancy in the results of our study with this study may be due to difference in characteristics of the control group19.
In our study we had lower fertilisation rate in group A than group B. This may be due to higher number of women with advanced age in group A (Table-1). As adenomyosis is known to occur in older women, we could not avoid this mismatch. However, we clarified that this effect did not influence the pregnancy rate by logistic regression analysis (Table-8). Stanekova et al performed a retrospective cohort study of 171 women who conceived after single euploid blastocyst transfer. In that study, 34 women had adenomyosis by TVS and 137 had morphologically normal uterus. Adenomyosis group had significantly higher miscarriage rates than the non- adenomyosis group (53% vs.19.7%; P = < 0.0001)29. Chiang et al performed a case control study in which 19 women with adenomyosis diagnosed by USG and 144 age matched controls with sonographically normal uterus. There was no significant difference in the pregnancy rates in fresh cleavage stage (day2/3) embryo transfers, but spontaneous miscarriages were increased in adenomyosis group: 4 (66.7%) vs. 8 (21%)18. In our study, the miscarriage rates were higher in the Group A compared to Group B but did not reach statistical significance probably due to small numbers (Table-6).
Overall though our study is of retrospective in nature, it has the following observations that would merit concern: adequate sample size, the study groups were comparable in number and baseline characteristics, the control group included women with exclusively tubal factor infertility and did not include those with other factors that are likely to affect the implantation. Moreover it addresses a specific group of women with adenomyosis who underwent fresh embryo transfer contrary to the recommended practice but with justifiable reasons. It is obvious from our results that the fresh transfer live birth rate was significantly affected in women with adenomyosis (Table 6). But a live birth rate of 17% was clinically reassuring in women with adenomyosis in situations where freeze-all would not be acceptable by patients due to increased cost for embryo freezing, and/or low number of good quality embryos which would not render the freezing cost-effective. However the cost-effectiveness of this approach needs to be evaluated prospectively on a larger data.