Professor and Chair, Department of Obstetrics and Gynecology, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo

Dr. Rebar reports no financial relationships relevant to this field of study.

SYNOPSIS: No decreases in implantation rates and live birth rates were present in a retrospective study from a single fertility center examining outcomes of in vitro fertilization in women with an arcuate uterus.

SOURCE: Surrey ES, Katz-Jaffe M, Surrey RL, et al. The arcuate uterus: is there an impact on in vitro fertilization outcomes after euploid embryo transfer? Fertil Steril 2018;109:638-643.

The arcuate uterus is one of the most common congenital uterine anomalies. Although, generally, it is believed that the arcuate uterus does not affect fertility, data are scanty and conflicting. Confusing the issue even more is the fact that there is no standardized definition for an arcuate uterus. Despite these difficulties, investigators at a single in vitro fertilization (IVF) center conducted a retrospective review of consecutive patients undergoing IVF and comprehensive chromosomal screening (CCS), with subsequent transfer of thawed euploid embryos in a later artificial menstrual cycle during the 2014 calendar year, to examine the effect of an arcuate uterus on implantation and live birth rates. They chose to include only individual patients undergoing CCS to control for the possible confounding variable of embryo aneuploidy. In addition, as part of their evaluation, all patients underwent three-dimensional ultrasound examination and office flexible hysteroscopy performed in the early follicular phase. An arcuate uterus was defined as existing when the myometrium extended perpendicularly below an interstitial line connecting the cornua on ultrasound by 4 to 10 mm with a myometrial angle > 90 degrees and was confirmed by hysteroscopy. This definition was based on a recent practice committee guideline from the American Society for Reproductive Medicine (ASRM).¹

Eighty-three transfer cycles were performed in 78 patients with an arcuate uterus, and 378 transfer cycles were performed in 354 women with a normal uterine cavity. In the women with an arcuate uterus, the mean depth of the fundal indentation was 5.43 ± 1.81 mm (standard deviation), with a range of 4 mm to 9.5 mm. The two groups did not differ regarding age or follicular reserve as assessed by anti-Müllerian hormone levels, follicle-stimulating hormone levels on cycle day 3, or antral follicle count. Similarly, there were no differences in numbers of blastocysts biopsied, percentage of euploid embryos (~59%), or numbers of euploid embryos transferred (~1.5 per transfer). There were no differences in outcomes either. The live-birth rate (defined as the number of live births > 26 gestational weeks per embryo transfer procedure) was 68.7% in women with an arcuate uterus and 68.7% in those with a normal uterus. The implantation rate (defined as the number of gestational sacs with ultrasound evidence of cardiac activity per number of embryos transferred) was 63.7% in women with an arcuate uterus and 65.4% in the control group (normal uterus). Spontaneous miscarriages after ultrasound visualization of a gestational sac also did not differ between the two groups (4.8% vs. 4.3%).

COMMENTARY

Although far from perfect, these are perhaps the best data yet suggesting that the presence of an arcuate uterus should be treated as an incidental finding without any effect on fertility, miscarriage rates, or the outcomes of pregnancy. One editorialist noted several reasons to question the findings.² The women in this study had mild anomalies, even with the definition of the arcuate uterus used. The patients were highly selected, being infertile and undergoing IVF. The method of defining an arcuate uterus by ultrasound required skill on the part of the examiners, and there is no real way to confirm the presence of an arcuate uterus by office hysteroscopy. Still, the findings agree with many but not all studies examining outcomes in women with an arcuate uterus.

The difficulty rests in distinguishing an arcuate from a septate uterus. The ASRM practice guideline defined a septate uterus as one with an acute angle of < 90 degrees at the central point of the septum (to differentiate from the obtuse angle of > 90 degrees seen with an arcuate configuration) and with the length of the septum > 1.5 cm. The guideline left undefined those individuals with a septum extending perpendicularly from a line between the cornua that is > 1.0 cm and < 1.5 cm in length. It is just this ambiguity that confuses the literature. As noted within the guideline, the septate uterus has been associated with increases in the risks of miscarriage, premature delivery, and malpresentation, but there is insufficient evidence to associate a septum with infertility.² Variations in definitions distinguishing arcuate from septate uteri may well account for some studies, such as one meta-analysis reporting that arcuate uteri are associated with increased incidences of both second trimester loss (pooled risk ratio, 2.39) and fetal malpresentation at delivery (pooled risk ratio, 2.53).³

We all recognize that uterine anomalies constitute a spectrum of disorders extending from the normal to the arcuate to the septate and finally to the bicornuate uterus and uterus didelphys. Surrey et al demonstrated that minor abnormalities indeed are trivial and are unlikely to affect fertility and the outcomes of any resulting pregnancies. We must await further studies using three-dimensional ultrasound and MRI to define just when a uterine anomaly becomes clinically significant. Even then, it may well be that there is no sharp limit separating uterine malformations that affect fertility and pregnancy and those that do not. However, it is clear that surgical correction of all uterine malformations is not required.

REFERENCES

1. Practice Committee of the American Society for Reproductive Medicine. Uterine septum: A guideline. Fertil Steril 2016;106:530-540.
2. Donnez J. Arcuate uterus: A legitimate pathological entity? Fertil Steril 2018;109:610.
3. Chan Y, Jayaprakasan K, Zamora J, et al. Reproductive uterine outcomes in women with congenital uterine anomalies: A systemic review. Ultrasound Obstet Gynecol 2011;38:371-382.