The authors are Dr. Pietro Gambadauro and Professor Antonio Pellicer.

Transcription

1 Welcome to chapter 8. The following chapter is called Fibroids and Infertility. The authors are Dr. Pietro Gambadauro and Professor Antonio Pellicer. ALT: Please use the navigation bar at the bottom of the viewing panel in order to proceed through, pause or go back through the lesson and to adjust the narration volume. Also please note the tabs above this panel which allow you to change the sidebar view and search for specific terms within the lesson text and narration transcript. 1

2 The objective of this lecture is to provide relevant data on the relationship between fibroids and infertility This information should be used to counsel infertile patients with fibroids 2

3 3 Fibroids are the most common benign tumour of the uterus. Most patients with fibroids are asymptomatic and the diagnosis is often accidental. Possible symptoms include: Abnormal uterine bleeding Pelvic pressure Compression of adjacent organs Pain

4 4 Treatment of fibroids is commonly indicated when symptoms are present or when the tumour is rapidly growing Different treatment modalities nowadays exist. While medical treatment only gives short term benefits, surgical removal (better if minimally invasive, i.e. through hysteroscopy or laparoscopy) is still the gold standard Alternative treatment modalities include embolization, laparoscopic myolisis and magnetic resonance guided focused ultrasound

5 5 Although the relationship between fibroids and infertility is still controversial, this association is becoming increasingly relevant because of the delay in childbearing in our society Today infertile women are more likely to present with fibroids, mainly because of their age

6 6 Nevertheless, it is unclear how fibroids might interfere with fertility, although several mechanisms are hypothesized These possible mechanisms include: Anatomical distortion Abnormal uterine contractility Inadequate blood supply to the endometrium Local inflammation/hostile endometrial environment

7 7 Fibroids can determine anatomical distortion of the female genital tract, that interferes with gametes and embryos transport This mechanism can be evident when fibroids cause obstruction or compression of the fallopian tubes or the cervical canal

8 8 Abnormal uterine contractility may be another mechanism by which fibroids might interfere with gamete and embryo transport, and also with implantation and early pregnancy development

9 9 Fibroids could cause an inadequate blood supply to the endometrium, which can interfere with embryos' implantation and placentation

10 10 Local inflammation or alteration of gene expression induced by the presence of fibroids can cause an endometrial environment which is hostile to embryo implantation

11 11 All these mechanisms can disrupt the reproductive function at different levels For instance, patients with fibroids could face reduced pregnancy rates, as well as an increased chance of miscarriage and obstetrical complications This lecture is mainly focusing on implantation, and therefore pregnancy rates

12 12 The interference of fibroids on fertility largely depends on their location and relation to the uterine cavity. Submucous, subserosal, and intramural fibroids can impact fertility differently The number and size of fibroids can also be a factor

13 13 By analyzing the results of in vitro fertilization on patients with fibroids, current medical literature shows how fibroids that are submucous or intramural with distortion of the uterine cavity reduce implantation and clinical pregnancy rates, while increasing miscarriage rates For example, in a 2008 review by Klatsky et al., patients without fibroids had a significantly higher implantation rate than patients with submucous fibroids. Patients without fibroids had a higher clinical pregnancy rate, and a 50% lower spontaneous abortion rate than patients with submucous fibroids

14 Possible mechanisms of submucous fibroids' detrimental effect on reproduction include anatomical factors, abnormal contractility or blood supply, and a hostile endometrial environment, as demonstrated by the recent finding of a global decrease in HOX gene expression in uteri with submucous fibroids Given the data available on the relationship between submucous fibroids and infertility, surgery (minimally invasive when feasible) should always be considered for infertile patients with fibroids that distort the uterine cavity 14

15 15 There is no data supporting the influence of subserous fibroids on fertility, thus surgery is not recommended in patients unless symptoms or specific anatomical disturbances exist

16 16 The relationship between intramural fibroids not distorting the uterine cavity and infertility is more controversial and complex Several parameters, including size, number, and location, need to be considered along with other clinical factors

17 17 Based on the model of in vitro fertilization, in which embryos are replaced into the uterine cavity, some authors have found an adverse effect of intramural fibroids on IVF outcome, whereas others have found no significant impact

18 18 Intramural fibroids that do not distort the endometrial cavity might disrupt the junctional zone within the myometrium, affecting general uterine function at the initial stages of embryo invasion, and later placentation

19 No agreement exists on the impact of fibroid size on reproductive outcomes. Some authors, for instance Khalaf et al., describe a negative effect of fibroids regardless of size, while others found that only larger fibroids with a diameter of more than 4 cm affect in vitro fertilization results. 19

20 20 Currently, as reported by Somigliana et al. in their 2007 review, myomectomy (better if laparoscopic) is commonly indicated when intramural fibroids have a diameter of 5 cm or more

21 Available literature on the relationship between intramural fibroids not distorting the cavity and infertility is frequently inconsistent for different reasons: First, it is difficult to study the mechanisms by which such a relationship should work Second, studies on fibroids and IVF have recognized biases, such as patients age and the effects of COH on endometrial receptivity Third, the impact of the size and number of fibroids has rarely been analyzed For those reasons, and also to improve the understanding of mechanisms involved in the fibroids-fertility interaction, we have recently published a paper based on 2 different studies 21

22 We have studied the relationship between intramural fibroids not distorting the cavity and infertility through 2 different studies: A prospective functional genomics study A large retrospective clinical study 22

23 We have studied the mechanism through a gene expression analysis during the window of implantation in women with and without intramural fibroids not distorting the cavity Only 3 of the 25 genes related to implantation were disregulated in patients with fibroids. This suggests that intramural fibroids do not interfere with implantation by disregulating relevant gene expression 23

24 For our retrospective clinical study, we chose egg-donation IVF as our model, in order to reduce the biases of patient (and oocyte) age and COH influence on endometrial receptivity. Additionally, we analyzed results depending on fibroid sizes and numbers A total of 1035 egg donation cycles were studied, including patients with small, large, and multiple fibroids, as well as 2 control groups (previous myomectomy and patients with no fibroid history) 24

25 25 As a result of our study, we observed that term pregnancy rates were not different among the established groups Therefore, we concluded that intramural fibroids not distorting the cavity do not have any effect on oocyte donation outcome, regardless of their size or number

26 26 To conclude, uterine fibroids are an increasingly common finding in infertile women. Our attitude must take into account the current knowledge on fibroids role in infertility, as well as the potential risks of surgery

27 27 Submucous fibroids, as well as intramural fibroids distorting the cavity, have been shown to interfere with fertility and assisted reproductive technology outcomes, and therefore their surgical removal should always be considered Subserosal fibroids, on the contrary, do not commonly need to be removed if asymptomatic Intramural fibroids which do not distort the cavity are commonly removed when greater than 5 cm

28 28 It is unclear how intramural fibroids might interfere with fertility, although our recent functional genomics study excludes a global alteration of the expression of genes involved in endometrial receptivity On the other hand, our clinical study demonstrates that fibroids do not interfere with egg donation results, regardless of their number and size This information should be taken into account when counselling infertile patients with fibroids

29 29 Answer: C

30 30

31 31 answer: B

32 32 answer: B

33 33 answer: D

34 34 answer: C