Newsletter

Table of Contents

23.01.2008

Newsletter No. 1/2008

Hydrosalpinx and IVF
A comparison of uterine peristalsis in women with normal uteri and uterine leiomyoma by cine magnetic resonance imaging.
Factors affecting reproductive outcome following abdominal myomectomy.
Myomas, pregnancy outcome, and in vitro fertilization.
Fibroids and in-vitro fertilization: which comes first.
Effect of fibroids on fertility in patients undergoing assisted reproduction. A structured literature review.
Fibroids and female reproduction: a critical analysis of the evidence.

1. Hydrosalpinx and IVF

This In vitro study was conducted to determine the effect of hydrosalpinx fluid on the expression of HOXA10, an essential regulator of endometrial receptivity. In patients with unilateral or bilateral hydrosalpinx fluid of the hydrosalpinx was aspirated from 10 patients at laparoscopy. The fluid was serially diluted in minimum essential medium. Ishikawa cells (an endometrial adenocarcinoma cell line, representative of endometrial epithelium) were incubated with this fluid at concentrations of 10% and 50% for 48 hours. Cells were also incubated in undiluted minimum essential medium (MEM) and in 10% serum as controls. After incubation, the cells were lysed in Trizol, and total RNA was extracted and analyzed by Northern blot using a 32P-labeled HOXA10 riboprobe. A 32P-labeled G3PDH probe was used as a control for loading. HOXA10 mRNA expression in endometrial cells decreased with increasing concentrations of hydrosalpinx fluid. Densitometric analysis of the northern blot revealed that HOXA10 mRNA expression was different from control at both concentrations (P<.007). HOXA10 is necessary for implantation in the murine model. HOXA10 expression is diminished by hydrosalpinx fluid. This effect on HOXA10 is a potential molecular mechanism by which implantation rates are diminished in women with hydrosalpinges. In a subsequent study salpingectomy increased peri-implantation endometrial HOXA10 expression in women with hydrosalpinx.

Daftary GS, Taylor HS. Hydrosalpinx fluid diminishes endometrial cell HOXA10 expression. Fertil Steril. 2002 Sep;78(3):577-80

Daftary GS, Kayisli U, Seli E, Bukulmez O, Arici A, Taylor HS. Daftary GS, Kayisli U, Seli E, Bukulmez O, Arici A, Taylor HS. Salpingectomy increases peri-implantation endometrial HOXA10 expression in women with hydrosalpinx. Fertil Steril. 2007 Feb;87(2):367-72. Epub 2006 Dec 14.

2. A comparison of uterine peristalsis in women with normal uteri and uterine leiomyoma by cine magnetic resonance imaging.

The non-pregnant uterus shows wave-like activity (uterine peristalsis). This pilot study was intended to determine: (1) whether uterine peristalsis during the menstrual cycle is detectable by cine magnetic resonance imaging (MRI); (2) the effects of leiomyoma on uterine peristalsis. Mid-sagittal MRI was performed sequentially with T2-weighted single-shot fast spin-echo (SSFSE) in 3 normal ovulatory volunteers and 19 premenopausal women with uterine leiomyoma. Direction and frequency of movement of the junctional zone were evaluated using a cine mode display. Junctional zone movement was identified in all subjects. Direction of uterine peristalsis in normal volunteers was fundus-to-cervix during menstruation, cervix-to-fundus during the periovulatory phase, and isthmical during the mid- and late-luteal phases. Abnormal peristaltic patterns were detected in three of five patients with uterine leiomyoma during menstruation and in the mid-luteal phase of the cycle, respectively. Cine MRI is a novel method for evaluation of uterine peristalsis. Results of this pilot study suggest that abnormal uterine peristalsis during menstruation and the mid-luteal phase might be one of the causes of hypermenorrhea and infertility associated with uterine leiomyoma.

Orisaka M, Kurokawa T, Shukunami K, Orisaka S, Fukuda MT, Shinagawa A, Fukuda S, Ihara N, Yamada H, Itoh H, Kotsuji F. A comparison of uterine peristalsis in women with normal uteri and uterine leiomyoma by cine magnetic resonance imaging. Eur J Obstet Gynecol Reprod Biol. 2007 Nov;135(1):111-5. Epub 2007 Feb 12.

3. Factors affecting reproductive outcome following abdominal myomectomy.

Fibroids may cause infertility and recurrent pregnancy loss. Studies have analysed the reproductive results after myomectomy according to the size, location and number of fibroids removed, but data are insufficient about comparison of opening the uterine cavity or not during surgery. Two hundred twenty-nine abdominal myomectomies with the indication of infertility and/or recurrent pregnancy loss were analysed retrospectively. The main purpose was to compare postoperative pregnancy, delivery and miscarriage rates according to either the uterine cavity was opened or not during the surgery. As a secondary outcome postoperative pregnancy rates were assessed by location, size and number of fibroids. There was no significant difference in reproductive results according to either the uterine cavity was opened or remained closed. Preoperative location, size and number of fibroids did not influence significantly the postoperative pregnancy rates. Opening the uterine cavity does not impair postoperative pregnancy rates. Preoperative location, size and number of fibroids do not influence postoperative reproductive results. Reference

Gavai M, Berkes E, Lazar L, Fekete T, Takacs ZF, Urbancsek J, Papp Z. Factors affecting reproductive outcome following abdominal myomectomy. J Assist Reprod Genet. 2007 Nov;24(11):525-31. Epub 2007 Nov 16.

4. Myomas, pregnancy outcome, and in vitro fertilization.

Uterine fibroids have been reported in 27% of infertile women, and 50% of women with unexplained infertility become pregnant after myomectomy. The age at which a first pregnancy occurs is increasing from the thirties to the forties. This increase and the recurrence rate of leiomyomas from 15 to 30% points to the effect of myomas on the infertility. Mechanisms by which myomas may cause infertility are abnormal uterine contractility, elongation of the uterine cavity, and distortion of uterine vascularization. Surgery may have beneficial or adverse effects without clear data on its effect on the assisted reproductive technology (ART) procedures. The present study was undertaken to establish the impact of surgical removal of myomas on fertility and infertility of patients undergoing ART procedures. Patients who underwent surgical removal of myomas before in vitro fertilization (Group A) had a cumulative success rate of 33% for one to three procedures (28 clinical pregnancies in 84 patients) and delivery rate of 25% (21 live births in 84 patients). Patients who underwent in vitro fertilization without previous surgery (Group B) had a 15% clinical pregnancy rate (13 pregnancies in 84 patients) (P < 0.05) and 12% delivery rate (10 deliveries in 84 pregnancies) (P < 0.05). Abortion rates were 7% (8 deliveries in 84 patients) and 4% (3 deliveries in 84 patients) in Groups A and B, respectively. This study confirms the beneficial effect of surgical removal of fibroids before undergoing ART procedures.

Bulletti C, DE Ziegler D, Levi Setti P, Cicinelli E, Polli V, Stefanetti M. Myomas, pregnancy outcome, and in vitro fertilization. Ann N Y Acad Sci. 2004 Dec;1034:84-92

5. Fibroids and in-vitro fertilization: which comes first.

The purpose of this review is thatthere is no consensus about the impact of uterine fibroids on fertility. This review explores past and recent studies that investigated the effects of submucosal, intramural, and subserosal fibroids on in-vitro fertilization (IVF) outcomes. We discuss the importance of proper evaluation of the uterus and endometrial cavity, and current options for optimal fibroid management in patients desiring fertility. Several studies have reviewed the data on fibroids and infertility, further exploring this potential relationship. Two recent studies investigated reproductive outcomes before and after myomectomy, and IVF outcomes based on fibroid size and location. Both studies concluded that fibroids can impair reproductive outcomes. Several papers thoroughly reviewed medical and surgical management options for patients with fibroids and desired fertility. Although several medical therapies may reduce fibroid volume or decrease menorrhagia, myomectomy remains the standard of care for future fertility. Recent data identified an increased rate of pregnancy complications after uterine artery embolization compared with laparoscopic myomectomy. A new procedure, magnetic resonance imaging-guided focused ultrasound ablation, shows promise for the management of symptomatic fibroids, and possibly for the management of fibroids prior to pregnancy. As with embolization, more data are needed to evaluate postprocedure fertility and pregnancy outcomes. Fibroid location, followed by size, is the most important factor determining the impact of fibroids on IVF outcomes. Any distortion of the endometrial cavity seriously affects IVF outcomes, and myomectomy is indicated in this situation. Myomectomy should also be considered for patients with large fibroids, and for patients with unexplained unsuccessful IVF cycles.

Rackow BW, Arici A. Fibroids and in-vitro fertilization: which comes first? Curr Opin Obstet Gynecol. 2005 Jun;17(3):225-31

6. Effect of fibroids on fertility in patients undergoing assisted reproduction. A structured literature review.

The aim of this study is to evaluate the current data to understand the impact of intramural leiomyomata on pregnancy outcome in assisted reproduction. In this review, articles were found by means of computerized Medline and Cochrane Library search using the key words uterine myomata, leiomyomata, fibroids, implantation, pregnancy, infertility and in vitro fertilization. Limitations were English, human, 1990-2002. Inclusion criteria were pregnancy data on in vitro fertilization, intramural myomata with no cavitary distortion and control groups without myomas for each patient with a myoma. There was a significant negative impact on implantation rate in the intramural myomata groups versus the control groups, 16.4 vs. 27.7% OR 0.62 (0.48-0.8). The delivery rate per transfer cycle was also significantly lower (myomata vs. control), 31.2 vs. 40.9% OR 0.69 (0.50-0.95). CONCLUSION: Our study supports the notion that patients with intramural fibroids have a lower implantation rate per cycle. The studies did not shed new light on the size of intramural myomata that could affect the outcome. In previous failed in vitro fertilization cycles, microsurgical removal of myomata must be considered.

Benecke C, Kruger TF, Siebert TI, Van der Merwe JP, Steyn DW. Effect of fibroids on fertility in patients undergoing assisted reproduction. A structured literature review. Gynecol Obstet Invest. 2005;59(4):225-30. Epub 2005 Mar 15.

7. Fibroids and female reproduction: a critical analysis of the evidence.

Observational epidemiological studies aimed at elucidating the relationship between fibroids and infertility are inconclusive due to methodological limitations. However, two main pieces of clinical evidence support the opinion that the fibroids interfere with fertility. First, in IVF cycles, the delivery rate is reduced in patients with fibroids but is not affected in patients who have undergone myomectomy. Second, even if randomized studies are lacking, surgical treatment appears to increase the pregnancy rate: approximately 50% women who undergo myomectomy for infertility, subsequently conceive. Available evidence also suggests that submucosal, intramural and subserosal fibroids interfere with fertility in decreasing order of importance. Although more limited, some data supports an impact of the number and dimension of the lesions. Drawing clear guidelines for the management of fibroids in infertile women is difficult due to the lack of large randomized trials aimed at elucidating which patients may benefit from surgery. At present, physicians should pursue a comprehensive and personalized approach clearly exposing the pros and cons of myomectomy to the patient, including the risks associated with fibroids during pregnancy on one hand, and those associated with surgery on the other hand.

Somigliana E, Vercellini P, Daguati R, Pasin R, De Giorgi O, Crosignani PG. Fibroids and female reproduction: a critical analysis of the evidence. Hum Reprod Update. 2007 Sep-Oct;13(5):465-76. Epub 2007 Jun 21

Gerhard Leyendecker