1 Fertility Centre, St Bartholomew's and The London Hospitals Trust, London EC1A, UK and 2 Department of Obstetrics and Gynaecology, St Bartholomew's and Royal London Hospitals School of Medicine and Dentistry, Queen Mary and Westfield College, Royal London Hospital, London E1 1BB, UK
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Abstract |
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Key words: IVF-embryo transfer/laparoscopic ovarian diathermy/polycystic ovarian syndrome
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Introduction |
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Since the efficacy of ovarian laparoscopic electrocauterization in the treatment of polycystic ovarian syndrome (PCOS) was first described (Gjonnaess, 1984), with ovulation in 92% of treated women and a pregnancy rate of 69%, the outcome of this treatment for clomiphene citrate (CC)-resistant anovulatory infertility in women with PCOS has been identified in many observational studies (Sumioki et al., 1988
; Gjonnaess, 1989
, 1994
; Gadir et al., 1990
; Kovacs et al., 1991
; Pellicer and Remohí, 1992; Amar and Lachelin, 1993
; Farhi et al., 1995
). Most investigators have found that laparoscopic ovarian diathermy or electrocautery results in a spontaneous ovulation rate of
50%, and a subsequent mean pregnancy rate of 50% in those who ovulate. It has been shown (Naether et al., 1994
) that these effects can be seen for up to 72 months after laparoscopic surgery, and it has also been reported (Gjonnaess, 1998
) that the majority (74%) among 51 of 165 women followed-up were still ovulating 1820 years after ovarian electrocautery. The value of laparoscopic ovarian diathermy has also been assessed in an attempt to reduce the risk of ovarian hyperstimulation syndrome (OHSS) in women undergoing IVFembryo transfer, ovarian diathermy being performed just before controlled ovarian stimulation (Rimington et al., 1997
; Egbase et al., 1998
).
Few data exist, however, on the outcome of IVFembryo transfer following laparoscopic ovarian diathermy in women with PCOS who underwent this procedure during their fertility management, yet failed to conceive. Thus, this retrospective study was conducted to compare ovarian stimulation and IVF outcome in 15 women with clomiphene-resistant PCOS who had previously undergone laparoscopic ovarian diathermy, with 16 control women with clomiphene-resistant PCOS who had not undergone such diathermy before IVF.
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Materials and methods |
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Fifteen of these women had previously undergone laparoscopic ovarian diathermy (group A), and 16 had not (group B). Monopolar diathermy had been performed in all cases. Two women had unilateral ovarian diathermy using four diathermy points (4 mm deep), and the remaining 13 had undergone bilateral ovarian diathermy using an average of six diathermy points (4 mm deep) in each ovary. All 31 women had clomiphene-resistant PCOS. Early follicular phase (day 3) serum concentrations of LH, FSH and testosterone were measured within 6 months of commencing the IVFembryo transfer treatment cycle in all women. Since all patients had either oligomenorrhoea or amenorrhoea, a withdrawal bleed was induced using medroxyprogesterone acetate (Provera, 5 mg b.d. for 7 days; Pharmacia and Upjohn, Milton Keynes, UK) before starting ovarian stimulation.
Ovarian stimulation was achieved by daily administration of gonadotrophins (human menopausal or recombinant FSH) following pituitary desensitization with a gonadotrophin-releasing hormone (GnRH) analogue for at least 14 days, starting on day 21. The starting dose of gonadotrophin was decided upon according to the clinical history, previous response to gonadotrophins, and features of each individual woman. Ovarian stimulation was monitored using transvaginal ultrasonography, and the dose of gonadotrophin adjusted according to the ovarian response. Human chorionic gonadotrophin (HCG, 10 000 IU) was administered when at least three follicles had reached a diameter of 18 mm. Oocyte retrieval was performed 36 h later under transvaginal ultrasound guidance and intravenous sedation. Luteal support was routinely administered in the form of progesterone pessaries (400 mg twice daily; Cyclogest, Hoechst, London, UK).
All oocytes were examined following insemination, and only those in which two pronuclei were visualized were considered to have fertilized normally. A maximum of three embryos were transferred 4872 h after oocyte recovery.
Statistical analyses were performed using the MannWhitney two-sample test to compare means, and the 2 or Fisher's exact test to compare frequencies. Differences were considered to be statistically significant if P
0.05.
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Results |
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In group A, 15 women underwent 22 cycles of ovarian stimulation for IVF, with eight undergoing one cycle and seven undergoing two treatment cycles. HCG was not given in four cycles (18.2%) because of failure to respond to ovarian stimulation. One patient had all embryos cryopreserved due to a high risk of developing OHSS, but despite this strategy was hospitalized with a moderate form of the condition (grade 3; Golan et al., 1989). Thus, 17 cycles (77.3%) were completed to an embryo transfer (Table II).
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No differences were observed between the two groups in the amount of gonadotrophin required for ovarian stimulation. A statistically significant higher percentage of follicles >14 mm in diameter was seen in group B than in group A (50.9 versus 36.3%, P < 0.0001) on the day of HCG administration, and while there appeared to be more oocytes retrieved in group B (14.3 ± 4.9 versus 11.8 ± 7.3), this was not statistically significantly different (Table II). There was, however, a statistically significant greater number of embryos available for transfer in group B than in group A (7.1 ± 3.8 versus 4.6 ± 2.7; P < 0.01) (Table II
). The pregnancy rate per cycle was similar in both groups, although the pregnancy rate per embryo transfer appeared much higher in group B (63.2 versus 41.2%) (Table III
), though this difference was not statistically significant. The miscarriage rate seemed higher in group B, with two miscarriages (28.6%) occurring in group A (one in the first trimester, one at 20 weeks gestation), whilst four miscarriages (66.7%) occurred in group B (two in the first trimester, two at 22 weeks gestation) (Table III
). This gave an apparently higher ongoing clinical pregnancy rate in group A (29.4 versus 10.5%), although the differences were not statistically significant.
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Discussion |
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Neither the mean number of oocytes retrieved nor the fertilization rate was statistically significantly different between the two groups, although there appeared to be more oocytes retrieved with a better fertilization rate in group B (14.3 ± 4.9 versus 11.8 ± 7.3; 51.2 versus 43.9%). This is consistent with an earlier report (Colacurci et al., 1997) in which IVFembryo transfer outcome was assessed in 23 women with PCOS following laparoscopic ovarian diathermy within 9 months of surgery. In this report, no significant differences were identified in the fertilization rate between women who had undergone ovarian diathermy before IVF and those who had not. In the present study, the apparently higher fertilization rate observed in group B women may be explained by the greater number of follicles of
14 mm diameter, which may have yielded more mature oocytes. However, despite more embryos being available in group B, two to three good grade embryos were available for transfer in both groups. The increased number of follicles of
14 mm diameter in group B compared with group A (50.9 versus 36.3%; P <0.0001) may be an indication of a subtle decrease in ovarian responsiveness following laparoscopic ovarian diathermy.
Mean serum LH concentrations in women who had undergone laparoscopic ovarian diathermy were found to be statistically significantly lower than before such diathermy (9.1 ± 4.9 versus 13.7 ± 6.3 IU/l; P < 0.05) (Table I), and also lower than mean serum LH concentrations in untreated women (9.1 ± 4.9 versus 14.6 ± 6.4, P < 0.05). The mechanism by which diathermy alters ovarian function is unclear. Typically, decreased androgen and LH concentrations, and increased FSH concentrations have been observed following surgery (Greenblatt and Casper, 1984; Amar et al., 1990
; Gadir et al., 1990
; Sakata et al., 1990; Rossmanith et al., 1991
). The reduction in serum LH concentration following laparoscopic ovarian diathermy is reported to be the main mechanism by which reproductive outcome is improved, with elevated concentrations being associated with a reduction in oocyte quality, fertilization rates and embryo quality (Stanger and Yovich, 1985
; Urman et al., 1992
), and higher miscarriage rates (Homburg et al., 1988
; Regan et al., 1990
). In this study, all women underwent the same pituitary down-regulation using a GnRH agonist, with consequent suppression of endogenous LH concentrations, for approximately 2 weeks before ovarian stimulation. This might explain the similar pregnancy rate per cycle (group A, 31.8% versus group B, 25.0%) and per embryo transfer (41.2 versus 63.2%), despite the difference seen in pretreatment LH concentrations. Likewise, others (Colacurci et al., 1997
) found no significant difference in the pregnancy rate per cycle or per embryo transfer between those women who had undergone laparoscopic ovarian diathermy and those who had not (32.1 versus 10.6% and 32.1 versus 12.2%), though they did identify a significantly better ongoing pregnancy rate per cycle (28.6 versus 7.3%, P < 0.05). Whilst no statistically significant differences were observed between the groups, there did appear to be an increased trend towards a higher miscarriage rate (28.6% in group A versus 66.7% in group B), and a lower ongoing pregnancy rate per cycle and per embryo transfer in group B (8.3 versus 22.7% and 10.5 versus 29.4%). However, statistical significance may not have been reached due to the small number of cycles studied (46 in the present study compared with 75 cycles studied by Colacurci et al.).
It was noted that the mean BMI for both groups was lower than might have been expected in women with PCOS (26.3 ± 3.6 in group A, 25.9 ± 4.0 in group B). A possible explanation for this might be the patient referral system that was operational in our hospital at the time of the study, the upper limit of BMI for inclusion into fertility treatment being 28 kg/m2.
Previously, a reduced trend for OHSS following laparoscopic ovarian diathermy has been observed (Colacurci et al., 1997). In the present study we observed a significant difference in multiple follicular development, with a greater percentage of the follicles produced being
14 mm in diameter in the untreated group (50.9 versus 36.3%; P < 0.0001), which may reflect an increased risk for OHSS. Although there was one case of moderate OHSS in group A, there were no cases of severe OHSS. This reduced potential for the development of OHSS in women who have undergone laparoscopic ovarian diathermy has also been described by others (Gadir et al., 1992
). Laparoscopic ovarian diathermy was also performed on 25 out of 50 women with polycystic ovaries following pituitary down-regulation just before receiving gonadotrophins for ovarian stimulation in an IVF cycle (Rimington et al., 1997
). These authors found the occurrence of moderate or severe OHSS to be higher in the untreated group, and proposed that laparoscopic ovarian diathermy would be a potentially useful treatment in women who have previously had an IVF cycle cancelled due to risk of OHSS, or who have suffered OHSS. Others (Egbase et al., 1998
) reported three women in whom unilateral laparoscopic ovarian diathermy was performed 35 weeks before IVFembryo transfer and who had previously developed moderate to severe OHSS as a consequence of ovarian stimulation. All three women were asymptomatic following ovarian stimulation, despite having received similar doses of gonadotrophin. The present study has not shown any significant differences between the two patient groups in terms of IVFembryo transfer outcome with respect to the pregnancy rate per cycle, or per embryo transfer. Laparoscopic ovarian diathermy may be associated with lower miscarriage rates and higher ongoing pregnancy rates per cycle and per embryo transfer, as suggested previously (Colacurci et al., 1997
). Laparoscopic ovarian diathermy may also have benefits for women undergoing IVFembryo transfer by possibly reducing the incidence of severe OHSS. Meanwhile, it is reassuring that the judicious use of ovarian diathermy does not appear to alter the outcome of IVFembryo transfer.
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Notes |
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References |
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Submitted on June 14, 2000; accepted on October 10, 2000.