Abstract

Hydrosalpinges have been associated with poor in-vitro fertilization (IVF) outcome in some, but not all, studies, perhaps through endometrial effects. To determine whether hydrosalpinges affect IVF outcome via endometrial factors alone, we analysed the results of recipients of donor oocytes with hydrosalpinges, thereby controlling for confounding variables, while isolating the intrauterine environment. We retrospectively analysed 110 patients who underwent 121 donor oocyte cycles in a university-based assisted reproduction programme. Thirteen cycles involving recipients (n = 10) with hydrosalpinges were compared to 108 cycles involving recipients (n = 100) without hydrosalpinges. Pregnancy, implantation, miscarriage, and ectopic pregnancy rates were compared between women with and without hydrosalpinges. There were no significant differences between the hydrosalpinx and no hydrosalpinx groups with respect to donor age, recipient age, or number or grade of embryos transferred. Patients with a hydrosalpinx had significantly lower embryo implantation rates (7.1 versus 19.3%, P < 0.05) and significantly higher miscarriage (75.0 versus 14.9%, P < 0.05) and ectopic pregnancy rates (33.3 versus 0.0%, P < 0.05) than normal controls. We conclude that the presence of a hydrosalpinx adversely affects early pregnancy events by altering the intrauterine environment.

Introduction

Several studies have shown an association between the presence of a hydrosalpinx and poor in-vitro fertilization (IVF) outcome (Andersen et al., 1994; Kassabji et al., 1994; Strandell et al., 1994; Vandromme et al., 1995; Katz et al., 1996; Fleming and Hull, 1996; Blazer et al., 1997). Akman et al. demonstrated a similar effect in cryopreserved embryos as well (Akman et al., 1996). Various theories have been proposed to explain this phenomenon. Sharara et al. suggested that chronic endometritis due to the same organism that caused the hydrosalpinx (i.e. Chlamydia trachomatis) leads to altered endometrial receptivity (Sharara et al., 1996). Others proposed that the initial infection permanently damaged the endometrium (Strandell et al., 1994). Mansour et al. postulated that reflux of fluid into the endometrial cavity could hinder implantation (Mansour et al., 1991). Retrograde spillage may also be embryotoxic (Mukherjee et al., 1996) or alter endometrial receptivity (Meyer et al., 1997). Alternatively, ovarian stimulation increases the fluid volume within the Fallopian tube (Mansour et al., 1991). Natural cycle IVF may decrease the fluid volume within the Fallopian tube and improve IVF success rates (Lindheim et al., 1997). Furthermore, hydrosalpinges may secrete cytokines that adversely affect pregnancy outcome (Grifo et al., 1989; Toth et al., 1992), through reflux of fluid, or via haematogenous or lymphatic routes.

Prior studies examining the effect of hydrosalpinges on IVF cycles have employed autologous oocytes. Using a donor oocyte model we sought to control for confounding variables, such as ovarian and uterine senescence, male factor, embryo quality and number, and the ovarian stimulation protocol with its effect on the endometrium. In this manner we effectively isolated the intrauterine environment so as to analyse early implantation events more accurately.

Materials and methods

A retrospective analysis of cycles (n = 13) was performed in 10 patients with hydrosalpinges and normal semen analyses undergoing IVF with donated oocytes in a university-based assisted reproductive programme. The presence of a hydrosalpinx was determined using either transvaginal ultrasonography or hysterosalpingography. These patients were then compared to others undergoing IVF with donated oocytes without hydrosalpinges and normal semen analyses (n = 100; 108 cycles).

Oocyte donors underwent ovarian stimulation with follicle stimulating hormone (FSH) and were monitored by transvaginal ultrasound and serum oestradiol concentrations (Sauer, 1995). When the follicles reached 18–20 mm, human chorionic gonadotrophin (HCG) was given to trigger ovulation. Thirty-six hours later follicles were aspirated transvaginally under ultrasound guidance. The oocytes were then incubated with spermatozoa. Fertilization was documented, and resulting embryos were transcervically transferred after 2 or 3 days to the recipient's uterus. Recipients were carefully synchronized with the donors to ensure the endometrium was appropriately primed for implantation. Synchronization was achieved with exogenous oestrogen and progesterone supplementation. Nine and 12 days after embryo transfer the patient was tested for pregnancy with serum HCG.

The two study groups were analysed for donor and recipient age, number and grade of embryos transferred. Measured outcomes included gross pregnancy rates (a positive β-HCG) and ongoing pregnancy rates (a documented fetal heart rate), as well as implantation, miscarriage, and ectopic pregnancy rates. The embryo implantation rate included only known intrauterine pregnancies. The ongoing pregnancy rate included only intrauterine pregnancies progressing beyond 12 weeks gestational age.

Statistics were performed with the SPSS statistical package. χ2 and Fisher's t-test were used. Significance was defined as a P value < 0.05.

Results

Results are shown in Table I. The hydrosalpinx group had a gross pregnancy rate similar to the group without hydrosalpinges. However, the implantation rate per embryo transferred in the hydrosalpinx group was significantly lower (P < 0.05) than the group without hydrosalpinges. Furthermore, the ectopic pregnancy rate and the miscarriage rate were significantly higher (P < 0.05) in women with hydrosalpinges. The ongoing pregnancy rate per embryo was significantly lower (P < 0.05) in those with hydrosalpinges as was the ongoing pregnancy rate per cycle. There were no significant differences between patients with hydrosalpinges and without hydrosalpinges related to donor age, recipient age, or number or grade of embryos transferred.

Discussion

In reviewing the data it is apparent that outcomes of donor oocyte cycles are negatively affected by the presence of a hydrosalpinx in the recipient. The initial pregnancy rates of the two groups studied were similar. However, women with hydrosalpinges had more ectopic pregnancies (P < 0.05), more miscarriages (P < 0.05), and a lower ongoing pregnancy rate (P < 0.05). All of these observations lessened the overall delivery rate of these patients, principally as a result of increased pregnancy wastage.

This study is unique in using a donor oocyte model to focus on the intrauterine environment. This model allows the dissociation of the donor's gametogenesis and steroidogenesis from the recipient's inherent endometrial receptivity and has been employed before to study isolated parameters that affect IVF outcome such as male factor (Gallardo et al., 1996) and ovarian and uterine senescence (Sauer, 1997). Because extrauterine factors were controlled for in this study, the adverse events appear to be mediated through alterations of the recipient's intrauterine environment.

The early survival of embryos and their ability to express HCG does not appear to be impaired in our study. In fact the presence of two ectopic gestations in the hydrosalpinx group underscores the notion that the tubal fluid itself is not embryotoxic. Deleterious effects are most apparent after weeks of observation, not days, which may reflect chronic endometrial changes rather than acute embryotoxic causes.

In the past we encountered few recipients with hydrosalpinges. More recently the indications for donor IVF have been expanded to include poor responders (Remohi et al., 1993) and failed IVF (Burton et al., 1993). Thus, we are noting a larger percentage of hydrosalpinges in this population.

This study confirms the deleterious effects of hydrosalpinges on IVF pregnancy rates. This effect is noted after weeks and suggests a chronic rather than acute process, which may reflect a chronic alteration of the endometrium rather than an embryotoxic effect of the tubal fluid. In our practice, patients are offered salpingectomy to remove the source of the noxious fluid. Although Shelton et al. (Shelton et al., 1996) have reported improved IVF outcome after salpingectomy, this approach still awaits controlled randomized trials to prove efficacy. Simply removing diseased Fallopian tubes may not reverse the chronic endometrial changes that lead to this phenomenon. Freeman et al. (Freeman et al., 1998) also noted an improvement in pregnancy outcome after salpingectomy, although a significant impairment of implantation remained. In addition, embryos that were not transferred were at greater risk of growth arrest and degeneration, suggesting a deleterious effect of the hydrosalpinx on the ovary as well. One possible alternative to salpingectomy is aspiration of the hydrosalpinx prior to IVF, which has shown benefit in some small series of patients (Russell et al., 1991; Van Voorhis et al., 1998).

Table I.

Results of donor oocyte in in-vitro fertilization cycles

 Hydrosalpinx No hydrosalpinx 
aP value < 0.05. 
Number of patients 10 100 
Number of embryo transfers 13 108 
Pregnancy rate/embryo transfer (%) 46.2 (6/13)  45.4 (49/108) 
Implantation rate/embryo transferreda (%)  7.1 (4/56)  19.3 (87/452) 
Ongoing pregnancy rate/embryoa (%)  1.8 (1/56)  16.4 (74/452) 
Ongoing pregnancy rate/embryo transfera (%)  7.7 (1/13)  39.8 (43/108) 
Ectopic rate/pregnancya (%) 33.3 (2/6)  0.0 (0/87) 
Miscarriage rate/implantation eventa (%) 75.0 (3/4)  14.9 (13/87) 
 Hydrosalpinx No hydrosalpinx 
aP value < 0.05. 
Number of patients 10 100 
Number of embryo transfers 13 108 
Pregnancy rate/embryo transfer (%) 46.2 (6/13)  45.4 (49/108) 
Implantation rate/embryo transferreda (%)  7.1 (4/56)  19.3 (87/452) 
Ongoing pregnancy rate/embryoa (%)  1.8 (1/56)  16.4 (74/452) 
Ongoing pregnancy rate/embryo transfera (%)  7.7 (1/13)  39.8 (43/108) 
Ectopic rate/pregnancya (%) 33.3 (2/6)  0.0 (0/87) 
Miscarriage rate/implantation eventa (%) 75.0 (3/4)  14.9 (13/87) 
1
To whom correspondence should be addressed
* Presented at the 1998 Annual Meeting of the Society of Gynecological Investigation, Atlanta, Ga, USA.

References

Akman, M.A., Garcia, J.E., Damewood, M.D. et al. (
1996
) Hydrosalpinx affects the implantation of previously cryopreserved embryos.
Hum. Reprod.
 ,
11
,
1013
–1014.
Andersen, A.N., Yue, Z., Meng, F.J. and Petersen, K. (
1994
) Low implantation rate after in-vitro fertilization in patients with hydrosalpinges diagnosed by ultrasonography.
Hum. Reprod.
 ,
9
,
1935
–1938.
Blazer, A.S., Hogan, J.W. and Seifer, D.B. (
1997
) The impact of hydrosalpinx on successful pregnancy in tubal factor infertility treated by in vitro fertilization.
Fertil. Steril.
 ,
67
,
517
–520.
Burton, G., Abdalla, H.I., Kirkland, A. and Studd, J.W. (
1993
) The role of oocyte donation in women who are unsuccessful with in vitro fertilization.
Hum. Reprod.
 ,
7
,
1103
–1105.
Fleming, C. and Hull, M. (
1996
) Impaired implantation after in vitro fertilisation treatment associated with hydrosalpinx.
Br. J. Obstet. Gynaecol.
 ,
103
,
268
–272.
Freeman, M.R., Whitworth, C.M. and Hill, G.A. (
1998
) Permanent impairment of embryo development by hydrosalpinges.
Hum. Reprod.
 ,
13
,
983
–986.
Gallardo, E., Simon, C., Levy, M. et al. (
1996
) Effect of age on sperm fertility potential: oocyte donation as a model.
Fertil. Steril.
 ,
66
,
260
–264.
Grifo, J.A., Jeremias, J., Ledger, W.J. and Witkin, S.S. (
1989
) Interferon gamma in the pathogenesis of pelvic inflammatory disease.
Am. J. Obstet. Gynecol.
 ,
160
,
26
–31.
Kassabji, M., Sims, J.A., Butler, L. and Muasher, S.J. (
1994
) Reduced pregnancy outcome in patients with unilateral or bilateral hydrosalpinx after in vitro fertilization.
Eur. J. Obstet. Gynecol. Reprod. Biol.
 ,
56
,
129
–132.
Katz, E., Akman, M.A., Damewood, M.D. and Garcia, J.E. (
1996
) Deleterious effect of the presence of hydrosalpinx on implantation and pregnancy rates with in vitro fertilization.
Fertil. Steril.
 ,
66
,
122
–125.
Lindheim, S.R., Heller, D., Ditkoff, E.C. and Sauer, M.V. (
1997
) Ovarian hyperstimulation compounds the deleterious effects of hydrosalpinx on outcome during IVF–ET.
Assisted Reprod. Rev.
 ,
7
,
64
–66.
Mansour, R.T., Aboulghar, M.A., Serour, G.I. and Riad, R. (
1991
) Fluid accumulation of the uterine cavity before embryo transfer: a possible hindrance for implantation.
J. In vitro Fert. Embryo Transfer
 ,
8
,
157
–159.
Meyer, W.R., Castlebaum, A.J., Somkuti, S. et al. (
1997
) Hydrosalpinges adversely affect markers of endometrial receptivity.
Hum. Reprod.
 ,
12
,
1393
–1398.
Mukherjee, T., Copperman, A.B., McCaffrey, C. et al. (
1996
) Hydrosalpinx fluid has embryotoxic effects on murine embryogenesis: a case for prophylactic salpingectomy.
Fertil. Steril.
 ,
66
,
851
–853.
Remohi, J., Vidal, A. and Pellicer, A. (
1993
) Oocyte donation in low responders to a conventional ovarian stimulation for in vitro fertilization.
Fertil. Steril.
 ,
59
,
1208
–1215.
Russell J.B., Rodriguez Z. and Komins J.I. (
1991
) The use of transvaginal ultrasound to aspirate bilateral hydrosalpinges prior to in vitro fertilization: a case report.
J. In vitro Fert. Embryo Transfer
 ,
8
,
213
–215.
Sauer, M.V. (
1995
) Oocyte donation; reviewing a decade of growth and development.
Semin. Reprod. Endocrinol.
 ,
13
,
79
–84.
Sauer, M.V. (
1997
) Infertility and early pregnancy loss is largely due to oocyte aging, not uterine senescence, as demonstrated by oocyte donation.
Ann. N.Y. Acad. Sci.
 ,
828
,
166
–174.
Sharara, F.I., Scott, R.T. Jr, Marut, E.L. and Queenan, J.T. Jr (
1996
) In-vitro fertilization outcome in women with hydrosalpinx.
Hum. Reprod.
 ,
11
,
526
–530.
Shelton, K.E., Butler, L., Toner, J.P. et al. (
1996
) Salpingectomy improves the pregnancy rate in in-vitro fertilization patients with hydrosalpinx.
Hum. Reprod.
 ,
11
,
523
–525.
Strandell, A., Waldenstrom, U., Nilsson, L. and Hamberger, L. (
1994
) Hydrosalpinx reduces in-vitro fertilization/embryo transfer pregnancy rates.
Hum. Reprod.
 ,
9
,
861
–863.
Toth, M., Jeremias, J., Ledger, W.J. and Witkin, S.S. (
1992
) In vivo tumor necrosis factor production in women with salpingitis.
Surg. Gynecol. Obstet.
 ,
174
,
359
–362.
Van Voorhis, B.J., Sparks, A.E., Syrop, C.H. and Stovall, D.W. (
1998
) Ultrasound-guided aspiration of hydrosalpinges is associated with improved pregnancy and implantation rates after in-vitro fertilization cycles.
Hum. Reprod.
 ,
13
,
736
–739.
Vandromme, J., Chasse, E., Lejeune, B. et al. (
1995
) Hydrosalpinges in in-vitro fertilization: an unfavourable prognostic feature.
Hum. Reprod.
 ,
10
,
576
–579.