Assessment of ovarian reserve in women undergoing cystectomy for benign ovarian disease

Abstract

Ovarian cystectomy is commonly performed to treat benign ovarian cysts, but might cause inadvertent damage to normal ovarian tissue, thereby influencing a woman’s ovarian reserve. Ovarian reserve is defined as the existent quantitative and qualitative supply of follicles which are found in the ovaries that can potentially develop into mature follicles which in effect determine a woman’s reproductive potential. It is commonly quantified by the levels of serum FSH and recently by total antral follicle count (2.0-10.0 mm follicles in both ovaries) and AMH levels. These tests however have inherent biological variation in relation to menstrual cycle and ageing; and are also influenced by the intra- and inter-observer variations. The aim of this thesis was to develop a reliable method of examining the effect of ovarian cystectomy on ovarian reserve. I began by examining the ultrasound markers of ovarian reserve. AFC is measured using 2D ultrasound and there is some evidence that 3D ultrasound can make more reliable counts than 2D. I examined the reliability of these two methods and compared them to a new 3D assisted method, SonoAVC which is designed to make automated AFC. I found that the intra- and inter-observer reliability of SonoAVC in counting the number of antral follicles was superior to 2D and 3D manual methods. It however required post-processing of the counts by manually clicking on the antral follicles initially missed in the automated version, thereby making it a semi-automated method. I then compared 2D ultrasound to SonoAVC in measuring the size of antral follicles as there is increasing evidence that the small antral follicles might be more predictive of ovarian reserve. I found that SonoAVC measured the size of antral follicles significantly quicker than 2D and also that the number of small follicles measured by 2D were more than SonoAVC, thereby raising the possibility that 2D might overestimate the number of small antral follicles. I then studied the ability of antral follicle counts stratified by size in prediction of ovarian response and pregnancy. I found that the small antral follicles measuring between 2.0-4.0 mm were independent predictors of clinical pregnancy and ovarian response to assisted reproduction treatment. I then examined the AFCs of different sizes made by SonoAVC and 2D in bovine ovaries and compared to the follicles obtained by manually dissecting the follicles. I found that SonoAVC with post-processing significantly underestimated and 2D overestimated the number of antral follicles measuring 4.0mm or less, but both made comparable counts of follicles measuring more than 4.0mm when compared with the antral follicles dissected manually. However, the agreement with SonoAVC with post-processing was more than that with 2D. Having established that SonoAVC albeit with post-processing was the most reliable method in measuring the size of antral follicles, I began to examine the intra- and inter-cycle variation and compared to AMH. I found that the small antral follicle measuring 2.0-6.0 mm showed least intra-and inter-cycle variation and that it was comparable to AMH. The larger antral follicles showed significant intra-cycle variation but a non-significant inter-cycle variation in the early follicular phase of menstrual cycle. I also examined the inter-ovarian variation in the AFC’s and found that the small antral follicles measuring 2.0-6.0 mm again showed the least variation between ovaries within an individual. I was finally able to conclude that small antral follicles (≤6.0mm) measured using SonoAVC were the most reliable in prediction of ovarian reserve, and showed excellent correlation with AMH. Finally, I examined the effect of laparoscopic ovarian cystectomy on the ovarian reserve for up to 6 months post-operatively using AMH and small AFC measured by SonoAVC. I found that ovarian cystectomy significantly reduces ovarian reserve and that this effect may be more pronounced with cysts of endometriotic nature, followed by dermoid cysts. In summary, the effect of ovarian cystectomy on ovarian reserve is best quantified using AFC of small follicles measuring less than 6.0 mm as it provides reliable measures of ovarian reserve, has minimal biological variation and is comparable to AMH