German Hospital IVF Unit, Bahceci Women Health Care Center, Istanbul, Turkey
1 To whom correspondence should be addressed at: Abdi Ipekci Cad, Azer Ishan, 44/7, Nisantas
, Istanbul, Turkey. Email: mbahceci{at}hotmail.com
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Abstract |
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Key words: endometrial fluid/IVF/PCOS/pregnancy/tubal factor
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Introduction |
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While it has been well documented that organic lesions inside the uterine cavity have a negative effect on IVF outcome, there are only few reports on the incidence and the impact of endometrial fluid accumulation visualized through ultrasonography during controlled ovarian hyperstimulation (COH) (Mansour et al., 1991; Sharara and McClamrock, 1997
; Sharara and Prough, 1998
; Levi et al., 2001
). In this study, we aimed to examine the impact of endometrial fluid accumulation first seen during ovarian stimulation on IVF outcome, and its association with the aetiology of infertility, in tubal factor infertility and PCOS patients specifically.
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Materials and methods |
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In our program, all patients are screened via hysterosonography for the presence of any organic lesion before entry to the IVF treatment. If a lesion is found, hysteroscopy is performed for both definitive diagnosis and treatment. In this study, all patients included were undergoing their first IVF trials. Those with suspicion of any lesion were excluded.
PCOS patients were diagnosed according to both their endocrine profile and ultrasonographic images, and tubal factor patients were identified mostly by hysterosalpingography and laparoscopy. Those with fluid accumulation comprised the study population, whereas all the other PCOS and tubal factor infertility patients comprised the control group. Patients with any co-existing infertility factor were not considered in the study.
All the patients were hyperstimulated using a down-regulation protocol of GnRH agonist (Lucrin; Abbott, Abbott Park, IL, USA) administered from midluteal phase at a dosage of 0.5 mg/day subcutaneously (s.c.) until menstruation and then at a dosage of 0.25 mg/day until HCG injection. After the assesment of pituitary down-regulation (serum estrogen level <50 pgml), exogenous gonadotrophin stimulation, including FSH or HMG, was given at a dose of 225 IU/day intramuscularly (i.m.) or s.c. Higher or lower initial doses were used if necessary. Follicular growth was monitored by assay of estradiol (E2) levels and ultrasonography. When two or more dominant follicles reached a mean diameter of 18 mm, i.m. HCG was administered at a dose of 500010 000 IU. Thirty-five hours later, oocytes were recovered transvaginally under ultrasound guidance. The fluid inside the uterine cavity or Fallopian tubes was never aspirated.
ICSI was performed in all cycles and on day 3 embryo transfer was carried out atraumatically using a Wallace catheter under ultrasound guidance with a full bladder. The number of embryos transferred was dependent on the age of the woman, the previous history and the embryo quality. Luteal support consisted of 50 mg progesterone in oil administered i.m. daily in all patients.
Clinical pregnancies were defined as the presence of gestational sacs recorded by ultrasonography. Abortions were defined as fetal losses before 12 weeks of gestation. We used the 2-test, Fisher's exact test and Student's t-test for normally distributed continous parameters, and the MannWhitney U-test for continous parameters of uncertain distribution. A P-value of <0.05 was considered statistically significant.
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Results |
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The cycle outcome of PCOS patients with or without the presence of endometrial fluid is depicted in Table I. The groups were comparable in terms of background characteristics, and no difference was detected in implantation, pregnancy and miscarriage rates.
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Discussion |
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We have shown that it is more common to see fluid accumulation inside the endometrium in IVF cycles of PCOS patients than tubal factor patients (22.3% versus 11.1%). We can only speculate about the mechanism of fluid accumulation inside the endometrial cavity. Regarding the mechanism in PCOS cases, in an earlier case report we presented a unique case of massive ascites before ovulation associated with gonadotrophin therapy (Akman et al., 1996). That case presented ascites before ovulation and was most likely due to an ovarian-mediated preovulatory effect of gonadotrophins on the peritoneal surface. Therefore, our case does not represent a case of ovarian hyperstimulation syndrome, but rather a greatly exaggerated peritoneal response to gonadotrophins. So, in milder forms this excess peritoneal fluid can drain into the uterine cavity through the patent Fallopian tubes. The cause of the difference in outcome between tubal factor and PCOS cases might be related to the source of the fluid. The drainage of the fluid from the peritoneal surface to the endometrial surface in PCOS could be envisaged as being more physiological, whereas in tubal factor cases it raises the suspicions of infectious origin of a previous tubo-ovarian disease.
Sharara and Prough (1998) reported four cases of endometrial fluid collection in women with PCOS undergoing ovarian stimulation for IVF. In the absence of any hydrosalpinx, these fluid collections were noted at day 5 of the stimulation. They found that the reproductive outcome when fluid collection was noted on the day of HCG or of embryo transfer was poor, and suggested that cryopreserving all embryos might be considered in these cycles. Contrary to that case series, in this study we found fluid collection inside the uterus to be more common in PCOS patients than tubal factor patients, and this did not affect the outcome, specifically in PCOS patients.
Oehninger et al. (1989) demonstrated that patients with tubo-ovarian disease present a decreased pregnancy rate per cycle and per transfer after IVFembryo transfer compared with patients with a previous tubal ligation. Also, hydrosalpinges have been reported to be able to enlarge during COH for IVF, with increased production of tubal fluid (Hill et al., 1986
). This fluid can drain into the uterine cavity and at times produce a vaginal discharge. Mansour et al. (1991)
reported three women presenting with hydrosalpinx and accumulation of fluid in the uterine cavity. The fluid was aspirated transcervically during oocyte retrieval in two cases, but reaccumulated at the time of the embryo transfer. None of the patients became pregnant, despite the transfer of four embryos in each case. The authors concluded that the accumulation of fluid rendered the cavity hostile to embryo implantation. In a large retrospective study (Katz et al., 1996
) we evaluated the effect of hydrosalpinx visualized by ultrasound in tubal factor patients and showed that it had a deleterious effect. Later, Andersen et al. (1996)
reported endometrial fluid and vaginal discharge as an indicator of poor outcome in IVF patients with hydrosalpinges. There are other reports mostly showing the same results (Zeyneloglu et al., 1998
). Also, Sharara and McClamrock (1997)
reported two cases of endometrial fluid collection in women with hydrosalpinx that was only noted after HCG administration. Levi et al. (2001)
evaluated 843 ART cycles in 721 patients and found that endometrial fluid was observed in 57 cycles during ovarian stimulation and in 12 cycles after HCG administration, with an overall incidence of 8.2% (69/843). Of these 57 cycles, a total of 27 cycles in which endometrial fluid developed (47.4%) involved non-tubal factor patients. Also, in the same study the authors evaluated 327 cycles involving tubal factor infertility patients and noted hydrosalpinges in 71 cycles (71/327; 21.7%); endometrial fluid collection developed in five of those cycles (5/71; 7%). They concluded that endometrial fluid collection during ovarian stimulation was associated with increased cancellation rates and lower pregnancy rates, and was not associated with ultrasonographically visible hydrosalpinges. In the current study there was fluid accumulation inside the uterine cavity in 19.0% of cases in the presence of uni- or bilateral hydrosalpinges. The rest might be due to hydrosalpinges that were not visible on ultrasound. We can only speculate about the mechanism by which hydrosalpinges affect implantation and pregnancy rates. Mechanical factors, the constant passage of fluid into the uterine cavity with or without its accumulation in the cavity, and embryotoxic factors may all play a role.
Although the fluid accumulation inside the cavity in PCOS patients appears not to affect IVF outcome, it has a deleterious effect in tubal factor patients. This is consistant with the findings of Bildirici et al. (2001). They found that the surgical treatment of communicating hydrosalpinges might improve endometrial receptivity as assessed by
v
3 integrin expression. Taking all these findings together one can consider that the mechanism in tubal factor patients is most probably through embryotoxicity rather than mechanical factors. Therefore, it might be reasonable either to occlude the proximal parts of the Fallopian tubes through cauterization or to remove the affected tube to block the drainage of this fluid. Strandell et al. (2001)
demonstrated, in a randomized controlled trial, an improved pregnancy outcome after salpingectomy had been performed prior to IVF in patients with hydrosalpinges large enough to be visible on ultrasound. In our program, during the study period surgery was suggested to all patients showing hydrosalpinx, but none of them accepted the procedure, probably due to the extra charges.
Although the number of cases is relatively small, the data reported here suggest that in PCOS patients, whenever any fluid accumulation inside the cavity is first seen during ovarian stimulation, as long as it does not return by the day of embryo transfer the transfer can be performed safely. However, in tubal factor infertility cases one should consider either cancellation of the cycle or cryopreservation of the embryos instead of transferring them.
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References |
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Submitted on March 29, 2004; resubmitted on July 13, 2004; accepted on December 13, 2004.
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