Semin Reprod Med 21(2):243-253, 2003. © 2003 Thieme Medical Publishers
There are many arguments to support the hypothesis that there is a causal relationship between the presence of endometriosis and subfertility. These arguments are reviewed in this article and include: (1) an increased prevalence of endometriosis in subfertile women compared with women of proven fertility; (2) a reduced monthly fecundity rate (MFR) in baboons with mild to severe (spontaneous or induced) endometriosis compared with those with minimal endometriosis or a normal pelvis; (3) a trend toward a reduced MFR in infertile women with minimal to mild endometriosis compared with women with unexplained infertility; (4) a dose-effect relationship: a negative correlation between the r-AFS stage of endometriosis and the monthly fecundity rate and crude pregnancy rate; (5) a reduced monthly fecundity rate and cumulative pregnancy rate after donor sperm insemination in women with minimal-mild endometriosis compared with those with a normal pelvis; (6) a reduced MFR after husband sperm insemination in women with minimal to mild endometriosis compared with those with a normal pelvis; (7) a reduced implantation rate per embryo after IVF in women with moderate to severe endometriosis compared with women with a normal pelvis; and (8) an increased monthly fecundity rate and cumulative pregnancy rate after surgical removal of minimal to mild endometriosis.
A causal relationship between endometriosis and infertility has not been definitely established. In women with moderate to severe endometriosis, pelvic adhesions may cause impairment of tubo-ovarian function and infertility. An inverse relationship between pregnancy rates and the degree of endometriosis has been proposed, but this has not been substantiated in prospectively controlled fertility trials. Subfertility associated with minimal to mild endometriosis is even more controversial. Nonhuman primates may offer valuable alternatives for prospective controlled fertility studies that cannot be performed in women for ethical reasons. The baboon has been documented as an interesting model in which to study laparoscopic and microscopic appearances, spontaneous evolution, pathogenesis, and fertility aspects of endometriosis.[1-4]
The aim of this review is to present the evidence available in the published literature supporting the hypothesis that endometriosis causes infertility in women and in nonhuman primates. The following questions are addressed:
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The prevalence of endometriosis in the general population is not exactly known. One study[5] estimated that there is a 10% prevalence of endometriosis in the general population, based on a single cohort study. This prevalence is close to the 8.3% prevalence calculated in earlier epidemiological studies, based on review of surgical and billing records of 21 different gynecologic surgeries.[6]
In women with infertility, the prevalence is highly variable, depending on selective use of laparoscopy in the infertility investigation and on the important bias of variable patient recruitment. Studies show that endometriosis can be found in 67 to 71%,[7] 43%,[8] 50%,[9] or 30%[10] of infertile patients. The proportion of infertile women with endometriosis who had moderate to severe endometriosis varied between 43%,[8] less than 19%,[9] and 27%.[10] The prevalence of minimal to mild endometriosis in infertile women was inversely correlated with body mass index; parous women were less likely to have endometriosis than nulliparous women.[11]
In women without fertility problems, the prevalence is unknown because these women are asymptomatic and do not have a laparoscopy. The best models to test the prevalence of endometriosis in fertile women are asymptomatic women undergoing tubal ligation (mostly women of proven fertility). The endometriosis prevalence ranges between 3 and 43%.[9,12-19] This high variability in reported endometriosis prevalence (Table 1) can be explained by several factors.
First, the prevalence may vary with the diagnostic method used: laparoscopy is generally accepted to be a better method for the diagnosis of minimal to mild endometriosis than laparotomy, and this technique has become widely available only during the last 15 to 20 years.
Second, the interest of the surgeon may play a significant role: minimal or mild endometriosis may be more eagerly looked for in a symptomatic patient under general anesthesia than during tubal sterilization in an asymptomatic patient. Even if pelvic inspection is performed carefully in the latter case, the local anesthesia that is more commonly used today limits surgery time and pelvic access.
Third, the experience of the surgeon in diagnosing the wide variability in appearance of especially subtle endometriosis implants, cysts, and adhesions is important. The concept of subtle endometrial lesions[20-22] and deep endometriosis[23] was reported only after 1985 and is not yet fully appreciated by all gynecologists who perform sterilizations.
Fourth, most studies evaluating the prevalence of endometriosis in women of reproductive age lack systematic histological confirmation of the macroscopic findings.[12-15,24-27] However, pathological confirmation of the laparoscopic impression is essential for the diagnosis of endometriosis,[28] notably for subtle lesions but also for typical lesions that have been reported to be histologically negative in 24%.[29] Furthermore, a study showed that the positive predictive value and specificity of visual laparoscopic diagnosis of pelvic abnormalities consistent with endometriosis versus histological diagnosis of endometriosis in patients with chronic pelvic pain were only 45% and 77%, respectively.[30]
Fifth, at the time of sterilization, parous women may have a variable time period since their last delivery, and most studies do not account for the bias that a longer time of uninterrupted menstrual cycles may lead to a higher risk of endometriosis development because of the effect of cumulative retrograde menstruation.[4]
Taking into consideration all of these limiting factors, it is nevertheless remarkable (Table 1 and Table 2)[87-98] that the prevalence of endometriosis seems to be higher in infertile patients (13% in 1970-1987; 33% in 1988-2000) than in previously fertile women at the moment of laparoscopic sterilization (8% in 1970-1987; 4% in 1988-2000). Table 3 shows that infertile women have a significantly higher prevalence of endometriosis (P < 0.0001) and are significantly more likely to have moderate to severe endometriosis (P < 0.0001) than previously fertile women. These data are confirmed in a study[31] showing a significant trend toward higher stages of endometriosis in infertile women whose husbands had normal sperm (stage II disease, 5.7% versus 3.3%; stage III disease, 3.1% versus 1.3%; stage IV disease, 6.4% versus 1.3%) than in women unable to conceive because they had not been exposed to sperm.
Therefore, we conclude that there is an increased prevalence of endometriosis in subfertile women compared with women of proven fertility and that there is also an increased prevalence of more advanced (moderate-severe) stages of endometriosis in subfertile women than in women of proven fertility.
Study Design
Ideally, this question could be addressed in a prospective observational
cohort study of two groups of patients without any fertility-impairing factors
who are similar with respect to age, sexual activity, socioeconomic class,
male fertility: one group with histologically proven endometriosis and one
without histologically proven endometriosis. In these groups the hypothesis
could be tested that the presence of endometriosis is associated with a lower
MFR and a lower CPR. Because this would imply a laparoscopy in these young
women before they even try to conceive, such a study will never be performed
for ethical reasons.
Because endometriosis occurs only in women and in nonhuman primates, such a study could be designed in a relevant primate model such as the baboon.[3] In two studies,[1,2] we demonstrated a normal MFR in baboons with spontaneous minimal endometriosis (18%) compared with baboons with a normal pelvis (24%). In one of these studies,[2] we also demonstrated that the MFR was significantly lower in baboons with mild, moderate, or severe endometriosis than in baboons with minimal endometriosis or a normal pelvis. An increased incidence and recurrence of luteinized unruptured follicle (LUF) syndrome were observed in baboons with mild endometriosis, suggesting that the reduced MFR could be caused by LUF syndrome.[32] In cynomolgus monkeys with induced moderate to severe endometriosis, impaired fertility has also been reported and has been attributed to LUF syndrome or to endometriosis-related adhesions.[33]
Another way to look at this issue in women is to compare the spontaneous MFR and spontaneous cumulative live birth rate (CLBR) in women from couples with unexplained infertility (control group) and in women with a normal fertility exploration (including normal male fertility) except for the presence of endometriosis. Unfortunately, most studies do not report MFR and CPR but report only pregnancy rate per patient.
Crude Pregnancy Rate. In a review,[34] it was reported that the combined spontaneous pregnancy rate in 2026 patients with unexplained infertility from 20 studies was 33% (95% confidence interval [CI], 31-35%). This seems similar[34] to the combined spontaneous pregnancy rate of 28% (95% CI, 23-33%) in untreated or placebo-treated women with minimal to mild endometriosis as possible fertility-reducing factor[35] from six randomized controlled trials.[36-41] Although these data suggest that there is no difference in crude pregnancy rate between the two groups, it needs to be stressed that the published data do not allow life-table analysis or the calculation of MFR and that it is not clear to which extent other fertility-enhancing therapy (e.g., ovulation induction, IUI, IVF) was used in both groups. Therefore, it is important to look at reported MFR and CPR in other studies.
Monthly Fecundity Rate. In another study evaluating the MFR in women with mild endometriosis after expectant management,[42] the MFR was 8.7% in patients with no other identifiable infertility factors, which is similar to the estimated MFR of 5%,[43] 10%,[44] 11%,[45] and 8%[46] in patients with mild endometriosis evaluated in other studies.[42] A similar low MFR of 6% was reported in women with minimal endometriosis submitted to expectant management with a CPR of 20, 30, and 47% after 3, 6, and 12 months, respectively.[47]
Cumulative Pregnancy Rate. A more detailed analysis of the ENDOCAN study[36] was published in a separate paper.[11] After exclusion of the women who received additional fertility treatment during the follow-up period after the diagnostic laparoscopy, the 36-week probability of conceiving and carrying a pregnancy beyond 20 weeks was 15.7% in women with minimal to mild endometriosis and 23.6% in women with unexplained infertility (adjusted fecundity rate ratio of 0.72, 95% CI, 0.45-1.17). Although not significant, this CPR was about 50% lower in women with minimal to mild endometriosis compared with those with unexplained infertility. No information was given on the MFR in these groups, but from the data it can be concluded that the MFR was 3.5% for women with unexplained subfertility and lower than 2.5% in women with minimal to mild endometriosis,[11] and this could be very close to statistical significance (Table 4). Although the authors concluded that there was no association between minimal-mild endometriosis and infertility, they acknowledged that a possible association might have been underestimated because of errors in the classification of the disease.[11] Other explaining factors could be that the study was underpowered to show a small but significant difference in MFR and CLBR between infertile women with minimal-mild endometriosis and those with unexplained infertility, or that minimal endometriosis is associated with normal fertility whereas mild endometriosis is associated with reduced fertility, as suggested by baboon studies[1,2] and by the endometriosis prevalence studies (reviewed earlier).
In advanced endometriosis, distortion of pelvic structures may lead to tubal obstruction or limited tubal mobility with reduced access to the ovarian surface at the time of ovulation. Although increased pregnancy rates have been reported after surgical therapy in patients with moderate to severe endometriosis when compared with expectant management, very few data are available, to the best of our knowledge, that document the spontaneous pregnancy rate, MFR ,or CPR in these patients. In an older study,[43] the overall crude pregnancy rate was 65% in 17 women with minimal endometriosis (mean duration of infertility: 3.3 years) with a median interval to pregnancy of 6 months (range 6 to 21 months). In contrast, the overall pregnancy rate was only 6.7% in 15 women with "varied degrees of endometriosis (mean duration of infertility: 3.4 years)" who had been offered and who had refused surgery.[43] Olive and coworkers[42] demonstrated an MFR of 3.1% in 123 infertility patients with mild to severe endometriosis managed expectantly for an interval of 1 to 25 months. The MFR in patients with mild, moderate, and severe endometriosis without other identifiable infertility factors was 8.7, 3.2, and 0%, respectively. The overall pregnancy rate in patients with mild, moderate, and severe endometriosis was 53, 25, and 0%, respectively.[42]
Other studies evaluating MFR and CLBR in patients with mild to severe endometriosis after expectant management[38,48,49] failed to make a clear distinction between the different stages of endometriosis in their outcome analysis. The MFR in patients with mild to moderate endometriosis was 3.1%.[48] The CPR in 14 women with endometriosis (11 with mild and 3 with severe endometriosis according to the Acosta classification[50]) was 56% after 1 year and 89% after 3 years.[49] The CPR in 14 women with minimal to severe endometriosis[51] was 46% after 30 months.[38]
In conclusion, these data suggest that the MFR is lower in patients with mild to severe endometriosis than in those with minimal endometriosis; that is, there seems to be a negative correlation between the MFR and the stage of endometriosis.
In a meta-analysis of 5214 cycles of high intrauterine insemination (IUI), using stepwise logistic regression, it was demonstrated[52] that the odds ratio for pregnancy associated with minimal to mild endometriosis was 0.45, significantly reduced (95% CI, 0.27-0.76) compared with women without endometriosis and as low as the odds ratio (0.48) for couples with male factor infertility (95% CI, 0.37-0.61). Furthermore, controlled prospective studies[53,54] have shown that the MFR and implantation rate per treated IUI cycle are significantly lower in women with minimal to mild endometriosis than in women with unexplained infertility (Table 5).
Fertility outcome after donor insemination is an important and attractive way to measure the effects of endometriosis on female fertility. This can be explained by the fact that ovulation induction (applied in most donor insemination programs) and the use of donor sperm reduce the variability associated with natural ovulation and husband sperm quality in spontaneous fertility trials.
Several uncontrolled studies[46,47] reported a normal MFR (20%) and a normal CPR (81%) after 12 cycles of donor insemination in women with minimal to mild endometriosis. However, controlled studies[55-57] have clearly indicated that after donor insemination both MFR and CPR are significantly reduced in women with minimal to mild endometriosis compared with women with a normal pelvis (Table 6).
This is a controversial issue that has been the subject of recent reviews.[58,59] It is difficult to pinpoint the effect of endometriosis on IVF outcome because it is well known that fertility outcome parameters after IVF are influenced by many variables including the woman's age, duration of infertility, cause of male/female infertility, previous pelvic surgery for endometriosis or other pelvic pathology, ovarian response to hormonal stimulation, morphological and genetic quality of gametes (egg and sperm) and embryos, and uterine and endometrial receptivity.
There seems to be consensus that women with moderate to severe endometriosis may have a lower response to ovarian stimulation.[60] This reduced ovarian sensitivity to external gonadotropins probably results from the presence of ovarian endometriotic cysts or from the reduced ovarian volume after surgical removal of endometriotic cysts.
The best way to assess the effects of endometriosis on fertility outcome after IVF is to look at the model of oocyte donation and reception. Women with moderate to severe endometriosis who receive donor eggs from women without endometriosis have a normal endometrial receptivity after IVF.[61] In contrast, eggs donated by women with moderate to severe endometriosis to women with a normal pelvis seem to have reduced quality, resulting in reduced embryo quality and reduced implantation rate per embryo.[59,62,63] These preliminary data suggest that endometriosis-associated subfertility is related to egg quality, not to endometrial receptivity.
In women with laparascopically diagnosed but untreated minimal-mild endometriosis COH with gonadotropins has been reported[64] to increase the cycle fecundity rate (15%, P < 0.04) compared with no treatment (4.5%).
Does the addition of IUI further increase the benefit from COH in these patients? One randomized controlled trial[65] in women with minimal to mild endometriosis demonstrated that superovulation with follicle-stimulating hormone (FSH) in combination with IUI resulted in a higher live birth per cycle (11%; odds ratio 5.6 with 95% CI, 1.8-7.4) and a higher cumulative live birth after four cycles (30%, P = 0.002) than no-treatment cycles (2 and 10%, respectively). The effectiveness of COH and IUI can be explained by the fact that ovulation is ensured and has become predictable, that more than one oocyte may be available for fertilization. It is also possible that, in women with minimal to mild endometriosis, the direct ovarian stimulation effect may correct deficient granulosa cell function[58] and improve oocyte maturation and embryo quality compared with nonstimulated cycles.
Until recently, there was considerable controversy regarding the association between minimal-mild endometriosis and subfertility. Laparoscopic destruction or excision of endometriosis had been reported to improve fertility in patients with minimal to mild disease by some[66-68] but not by other[44,69] investigators. It seemed possible that the MFR is higher during the first 6 to 12 months after laparoscopic surgery than after expectant management,[70,71] but no evidence existed that surgical treatment is superior to expectant management in the long term. Much better information is available today.
In a meta-analysis[72] it was reported that in women with minimal to mild endometriosis the odds ratio for pregnancy was 2.7 times higher after ablative surgery compared with no surgery or medical treatment. Furthermore, two randomized controlled trials[36,73] have tested the hypothesis that the fertility outcome is enhanced after surgical excision of minimal to mild endometriosis. The most important data of these two studies are summarized in Table 7. The only disadvantage of the Canadian multicenter study[36] is that patients were informed after surgery whether they had received surgical excision or diagnostic laparoscopy, and this information may have influenced their reproductive behavior. The fact that endometriosis-related adhesions were also removed, in addition to peritoneal endometriosis, does not compromise the findings of this study[36] because it is well known that women and baboons with mild endometriosis may have some filmy adhesions related to both peritoneal and adnexal lesions.[51,74,75] In contrast, the Italian study[73] can be criticized for several methodological weaknesses as reviewed in Table 7.
First, the study[73] was underpowered, including only 91 patients, compared with 341 patients in the Canadian study.[36]
Second, it is remarkable that the Italian study[73] included after randomization more patients undergoing surgical excision of endometriosis (n = 54) than patients undergoing diagnostic laparoscopy (n = 47), and no explanation is offered in the paper for this considerable difference in numbers after randomization.
Third, the duration of infertility was considerably longer in the Italian study[73] (4 years) than in the Canadian study[36] (2 years). It is well known that duration of infertility is a very important factor influencing both MFR and CPR independently of other causes of infertility. The bias introduced by the longer duration of infertility in couples participating in the Italian trial[73] may have reduced the possibility of finding any significant effect of surgical treatment, especially in view of the fact that there was no proper power calculation in the Italian study.
Fourth, the Italian study[73] did not present any data on MFR or CPR using life-table analysis but published only the crude live birth rate per patient, not controlled for number of cycles per patient or time of follow-up after surgery. It is well known that fertility outcome should be measured by more controlled variables such as MFR, CPR, or time to pregnancy.[42,70,76]
Fifth, 41 of the 91 patients in the Italian study[73] had received gonadotropin-releasing hormone (GnRH) analog treatment after surgery (18 from the surgical excision group, 23 from the diagnostic laparoscopy group). There was no specification of how long this medical treatment was given and how ovarian function was affected. Obviously, the lack of this information introduces another bias influencing fertility outcome.
Taking into account the relative methodological weaknesses of the Italian study[73] compared with the Canadian study,[36] extreme caution is needed before including these two studies together in a meta-analysis,[77] especially because the fertility outcome data are reported so differently. Therefore, it seems fair to stick to the data of the best study,[36] demonstrating that both MFR and CPR after 36 weeks are significantly higher and twice as high after surgical excision of minimal to mild endometriosis (4.7 and 30.7%, respectively) than after diagnostic laparoscopy (2.4 and 17.7%, respectively).
Another argument for surgical excision of minimal to mild endometriosis is the observation that, according to our current knowledge, in both women and nonhuman primates minimal to mild endometriosis is a progressive disease in at least 30 to 60% and it is impossible to predict in which patients disease progression will occur.[78] Indeed, during serial observations, deterioration (47%), improvement (30%), or elimination (23%) was documented over a 6-month period in women with initial minimal-mild endometriosis.[79] In another study, endometriosis progressed in 64%, improved in 27%, and remained unchanged in 9% over 12 months.[40] A third study[80] involving 24 women reported disease progression in 29%, disease regression in 29%, and no change over 12 months in 42%. Follow-up studies in both baboons[81,82] and women[83] with spontaneous endometriosis over 24 months have demonstrated disease progression in all baboons and in six out of seven women studied.
Women with moderate-severe endometriosis have more adnexal adhesions and larger endometriotic ovarian cysts than those with minimal-mild disease,[74] and these may result in reduced fimbrial efficiency to pick up the ovulated egg from the ovarian surface and in impaired tubal transport of eggs, sperm, and embryos. However, no randomized controlled trials or meta-analyses are available to answer the question of whether surgical excision of moderate to severe endometriosis enhances the pregnancy rate. Most studies present only crude pregnancy rates without detailed information regarding time of follow-up and are therefore not relevant.
Only a few studies are available evaluating the correlation between the stage of endometriosis and MFR or CPR using life-table analysis. More follow-up studies are needed to document the CPR after surgery for moderate to severe endometriosis, but these need to be controlled for the length of follow-up per patient and for other fertility-reducing factors such as female age, duration of infertility, male infertility, and postoperative fertility treatment with assisted reproduction. On the basis of three published studies[84-86] (Table 8), there seems to be a negative correlation between the stage of endometriosis and the spontaneous CPR after surgical removal of endometriosis, but statistical significance was reached in only one study.[86]
Based on the evidence presented in this article, many arguments support the hypothesis that endometriosis causes subfertility.
Reference Total N N (%) with Endometriosis Minimal-Mild Moderate-Severe Histological Confirmation Hasson, 1976[87] 296 4 (1.5) -- -- No Drake and Grunert, 1980[88] 43 2 (5) -- -- No Strathy et al, 1982[24] 200 4 (2) 4 0 No Liu and Hitchcock, 1986[12] 74 32 (43) 32 0 No Moen, 1987[13] 108 19 (18) 15 4 No Subtotal 1976-19[87] 721 61 (8) 51/54 (93%) 4/55 (7%) Kirshon et al, 1989[14] 566 42 (7.5) 28 4 No Wheeler, 1989[6] 3060 49 (1.6) -- -- No Trimbos et al, 1990[27] 200 5 (2.5) 1 4 No Moen and Muus, 1991[16] 107 24 (22) 23 1 Yes Mahmood and Templeton, 1991[15] 598 37 (6) 30 7 No Rawson, 1991[17] 8 4 (50) -- -- No Sangi-Haghpeykar and Poindexter, 1995[19] 3384 126 (3.7) 121 5 No Balasch et al, 1996[9] 30 13 (43) 13 -- No Subtotal 1988-2000 7953 300 (4) 216/239 (93%) 21/239 (9%) Total 8674 361 (4) 267/292 (91%) 25/292 (9%)
Reference Total N N (%) with Endometriosis Minimal-Mild Moderate-Severe Histological Conformation Peterson and Behrman, 1970[89] 204 70 (33) Duignan et al, 1972[90] 675 52 (8) Liston et al, 1972[91] 312 25 (8) Pent, 1972[92] 22 1 (5) Goldenberg and Magendantz, 1976[93] 112 29 (26) Hasson, 1976[87] 66 15 (23) No Cohen, 1976[94] 1380 320 (23) Musich and Behrman, 1982[95] 182 63 (35) Strathy et al, 1982[24] 100 19 (19) No Nordenskjold and Ahlgren, 1983[96] 433 69 (16) Chang et al, 1987[97] 2053 44 (2) Subtotal 1970-1987 5539 707 (13) Mahmood and Templeton, 1989[98] 490 101 Koninckx et al, 1991[7] 416 283 (68) 192 91 Yes Mahmood and Templeton, 1991[15] 654 133 (21) 86 47 No Gruppo Italiano, 1994[10] 660 195 (30) 142 53 Balasch et al, 1996[9] 52 26 (50) 21 5 Corson et al, 2000[8] 100 43 (43) 22 19 Subtotal 1988-2000 2372 781 (33) 463/678 (68%) 215/678 (32%) Total 7911 1068 (13.5)
Fertility Status Number Endometriosis Minimal-Mild Moderate-Severe Previously fertile 7953 300 (4%) 216 (91%) 21 (9%) Infertile 2372 781 (33%) 463 (58%) 215 (32%) P value P < 0.0001 P < 0.0001
Outcome Endo Stage I-II Unexplained Infertility Crude RR 95% CI CLPR > 20/52 within 36 weeks All recruited patients 18.15 23.66 0.77 0.52-1.15 After exclusion of patients with additional fertility treatment 15.7 23.6 0.66 0.45-1.17? MFR (per 100 person-months) All recruited patients 2.52 3.48 0.72 0.46-1.12 After exclusion of patients with additional fertility treatment <2.52 About 3.48 <0.72 ? Data based on Berube et al, 1998.[11]
Rate Reference Minimal-Mild Endometriosis Unexplained Infertility P Value Cycle fecundity rate Omland et al, 1998[53] 8/49 (16%) 40/119 (34%) < 0.05 Nuojua-Huttunen et al, 1999[54] 9/138 (6%) 63/413 (15%) 0.05 Implantation rate Omland et al, 1998[53] 9/49 (18%) 52/119 (44%) < 0.05
Rate Reference Minimal-Mild Endometriosis Unexplained Infertility P Value Cycle Hammond et al, 1986[56] 9/218 (4%) 38/196 (20%) < 0.05 fecundity rate Toma et al, 1992[57] 5/86 (6%) 29/212 14% (95% CI, 8-20%)
12% (46/380)< 0.05 Jansen et al, 1986[55] 2/56 (4%) < 0.05 Cumulative Hammond et al, 1986[56] 20% 55% pregnancy rate after 6 cycles Toma et al, 1992[57] 38% 80%
Parameter Endocan, 1997 GISE Italy, 1999 N patients included 341 91 (54 excision, 47 control) Duration infertility 2 years 4 years Postoperative GnRH analogs No Yes, n = 41 (18 excision, 23 control) MFR control group 2.4% No data MFR excision group 4.7% No data Rate ratio comparing MFR between groups 1.9 (95% CI, 1.2-3.1) No data CPR control group 17.7% No data CPR excision group 30.7% No data P value comparing CPR between groups P = 0.006 No data Live birth per patient (control group) No data 22% Live birth per patient (excision group) No data 20% P value comparing live birth per patient between groups No data NS MFR, monthly fecundity rate; CPR, cumulative pregnancy rate.
CPR Reference Stage of Endometriosis P value Minimal Mild Moderate Severe 1 year Guzick et al, 1997[85] 39% 31% 30% 25% NS 1 year Adamson et al, 1993[84] 45% 32% NS 1.5 years Osuga et al, 2002[86] 45% 28% < 0.05
Address for correspondence and reprint requests: Thomas M. D'Hooghe, M.D., Ph.D., Leuven University Fertility Center, Department of Obstetrics and Gynecology, University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium.
