**2.3.1 Materils and methods**

388 Endometriosis - Basic Concepts and Current Research Trends

endometriosis group vs. 2.0 ± 0.6 in the moderate to severe endometriosis group vs. 1.9 ± 0.5 in the tubal infertility group vs. 1.8 ± 0.6 in the unexplained infertility group; p>0.05). Surprisingly, when the data were analyzed according to the stage of endometriosis, in the group with moderate to severe endometriosis (stages III and IV) a significantly higher fertilization rate was observed compared to the group with minimal to mild endometriosis (stages I and II) (78.4% vs. 66.8%, respectively; p=0.001). However, implantation rates were low and not significantly different between these subgroups (5.5% in the group with moderate to severe endometriosis vs. 2.8% in the group with minimal to mild

Another study which failed to show negative impact of endometriosis on embryo quality was conducted by Swedish researchers (Bergendal et al., 1998). The analysis included a total of 65 IVF-ET cycles in 48 patients with endometriosis as the only apparent cause of infertility and 98 cycles in 98 patients in whom tubal factor was the only apparent cause of infertility (controls). The embryos were graded according to criteria set by the authors' center (morphology and cleavage stage) with embryo quality scores raging from 1 to 3, with 3 being the best score. The average score of the whole subgroup (defined as arithmetical average of all scores) was used in the final analysis. Despite the fact that fertilization rate was significantly higher in patients with tubal infertility compared to patients with endometriosis (78.3 ± 18.3% vs. 60.1 ± 31.7%, respectively; p=0.00001), no difference was noted in cleavage rates (87.9 ± 19.1% in the tubal factor group vs. 85.2 ± 22.1% in the endometriosis group; p=0.43) or morphological score of embryo for ET (2.5 ±0.39 in the tubal

In yet another study which reported results on the impact of endometriosis on embryo quality (Dmowski et al., 1995), a retrospective analysis of 237 consecutive IVF-ET cycles in patients with and without endometriosis was conducted. In the group without endometriosis, indications for IVF-ET were tubal disease, pelvic adhesions, male factor, unexplained infertility, ovarian dysfunction ant other factors. In this study, the number of oocytes cleaved was taken as the indirect measure of embryo quality. The authors reported there was no difference between groups in the number of fertilized and cleaved oocytes, but no exact numerical values for these variables were included in the published report. The lack of properly defined control group (endometriosis vs. all other indications) and the absence of further details on development of transferred embryos warrant caution for

We conducted a retrospective clinical study which encompassed 346 stimulated IVF or ICSI cycles with the transfer of one or two blastocysts performed at the Department of Reproductive Medicine and Gynecological Endocrinology at the University Medical Centre

The primary objective of our study was to examine possible differences in direct and indirect indicators of embryo quality between women with endometriosis as the only indication for the treatment and an adequate control group of women with tubal factor only. Possible differences in various other outcomes of IVF-ET cycles between these two groups

interpretation, at least in the segment of the study pertaining to embryo quality.

infertility group vs. 2.4 ± 0.4 in the endometriosis group; p=0.45).

endometriosis, p=0.46).

**2.3 Our study** 

of Maribor, Slovenia.

Data used in this analysis were received from the centre's database on couples treated for infertility from 2003 to 2010. If there any data for any variable was missing from the database, the patient's documentation (paper records) was checked. If it was still impossible to find the missing data, the patient was excluded from further analysis. Patients included were under 43 years of age and prior to entering an IVF/ICSI treatment, underwent all tests prescribed by the protocol for clinical examination of infertile couples.

The observed cycles were divided into two groups: 173 cycles were performed in patients with endometriosis as the only indication for treatment and 173 cycles in women with tubal factor infertility (control group). The patients from tubal factor group were individually matched with women with endometriosis by age group (<30, 30-34, 35-39, >39 years), number of retrieved oocytes (<5, 5 or more) and number of transferred embryos (1, 2 or 3).

Patients were most frequently stimulated according to the protocol involving gonadotrophin-releasing hormone agonists (GnRH-a) (almost exclusively using the long protocol). In the few remaining patients, the protocol with gonadotrophin-releasing hormone antagonists (GnRH-ant) was applied. GnRH agonists used were triptorelin (Diphereline®, Ipsen Pharma Biotech, France), gosereline (Zoladex®, Zeneca Pharmaceuticals, England) or busereline (Suprefact®, Sanofi Aventis, France). Cetrorelix (3 mg) (Cetrotide®, Merck Serono, Switzerland) was used as a GnRH antagonist. Follicle growth was predominantly stimulated by recombinant FSH (Gonal F®, Merck Serono, Switzerland), while human menopausal gonadotrophin (HMG) (Menopur ®, Ferring Pharmaceuticals, Switzerland) was used occasionally. On the day when at least two follicles reached an average diameter of 18 mm, final maturation of the oocyte was stimulated by the urinary human HCG (Profasi®, Merck Serono, Switzerland, using a dose of 10,000 IU) or human recombinant HCG (Ovitrelle®, Merck Serono, Switzerland, 250 mg dose). A detailed description of the laboratory procedures can be found elsewhere (Kovacic et al., 2009). Approximately 36 hours (36 ± 1) following the administration of HCG, oocytes were recovered by ultrasound-guided trans-vaginal follicle aspiration. Fertilization was performed through IVF or ICSI. Medicult® media (MediCult, Denmark) were used for oocyte culturing. Pursuant to the protocol of our centre, only one or maximally two blastocysts were transferred on the fifth, exceptionally on the fourth day following follicle aspiration. Labotec® catheter (Labotec, Germany) was used for blastocyst transfer. In line with the legislation in force at the time of the study, the couple was allowed to decide on the number of embryos to be transferred. Embryos were transferred only after both partners signed the official consent form for the transfer of embryos. A day after the follicle aspiration, all patients started receiving didrogesterone (30 mg/day) (Dabroston®, Belupo, Croatia) or micronized progesterone (600 mg/day) (Utrogestan®, Laboratories Besins International, France) for luteal support.

Quality of transferred blastocysts was evaluated by a blastocyst classification system based on morphological criteria, developed by our centre (Kovacic et al., 2004). This classification

Embryo Quality and Pregnancy Outcome in Infertile Patients with Endometriosis 391

undertaken to identify the subgroups of the same blastocyst quality score in which possible

B1 195 (24.8) 201 (25.2) 0.873 B2 54 (6.9) 70 (8.8) 0.161 B3 106 (13.5) 114 (14.3) 0.653 B4 85 (10.8) 71 (8.9) 0.198 B5 47 (6.0) 46 (5.8) 0.851 B6 105 (13.4) 140 (17.5) 0.022 B7 41 (5.2) 25 (3.1) 0.038 B8 153 (19.5) 132 (16.5) 0.127

Since a significant difference was present only in the subgroups of transferred blastocysts of very low quality (scores B6 and B7), this finding doesn't provide any further insight into the

Analysis of indirect embryo quality indicators showed no statistically significant differences

**Tubal factor group (N=173)**

**Tubal factor group (N=173)** 

> **Tubal factor group (N=173)**

**P value** 

**P value** 

**P value** 

significant difference was present. The results are presented in Table 1.

**Endometriosis group (N=173)**

Total 786 (100.0) 799 (100.0)

between the groups. The results are presented in Table 2.

differences between the groups. Results are presented in Table 3.

**The outcome Endometriosis group** 

\*Biochemical pregnancies and clinical miscarriages combined

differences were noted between the groups.

**Variablea Endometriosis group** 

a Data are expressed as mean ± standard error.

Table 1. Comparison of embryo quality scores between the studied groups

**(N=173)** 

No. of embryos on Day 2 7.5 ± 0.30 7.5 ± 0.29 0.890 No. of blastocysts 3.7 ± 0.21 4.0 ± 0.20 0.317 No. of frozen blastocysts 2.0 ± 0.18 2.4 ± 0.20 0.210

Table 2. Comparison of indirect indicators of embryo quality between the studied groups.

**(N=173)** 

Implantation rate (%) 40.6 (112/276) 47.1 (130/276) 0.123 Clinical pregnancy rate (%) 49.7 (86/173) 54.3 (94/173) 0.389 Clinical miscarriage rate (%) 4.6 (8/173) 6.4 (11/173) 0.479 Early pregnancy loss\* rate (%) 8.7 (15/173) 11.6 (20/173) 0.373 Live birth rate (%) 40.0 (64/173) 45.1 (74/173) 0.351

In the additional analysis of some of the other important parameters, no significant

Table 3. Comparison of IVF-ET cycles outcomes between the studied groups

Analysis of outcomes of IVF-ET cycles also failed to show any statistically significant

**Blastocyst quality** 

**score** 

problem.

is a modification of the earlier, well established blastocyst evaluation system (Gardner & Schoolcraft, 1999). The classification used in our laboratory takes into consideration four parameters: blastocoel expansion, inner cellular mass (ICM) form, morphology and cohesion of the trophoectoderm (TE) as well as the degree of embryo fragmentation. There are 8 grades of quality of blastocysts (B1 to B8) in this system, with B1 being the best quality score and B8 the worst. The data on blastocyst quality expressed in this way had to be transformed before entering the statistical model. The transformation was performed in two steps. First, the blastocysts from B1 category were designated as optimal quality blastocysts, while those in categories B2–B8 were classified as being of suboptimal (non-optimal) quality. In the second step, in cases where blastocysts of different quality were transferred, the subgroup with blastocysts of different quality was merged with the subgroup in which all transferred blastocysts were of optimal quality. In this way, for the final statistical analyses we had a subgroup with blastocysts of suboptimal quality only and a subgroup with at least one blastocyst of optimal quality. All other possibilities for regrouping were also tested, but it was concluded that the chosen transformation of data showed the best fit with this model. This conclusion was expected, because it was in line with the assumption that in those cases in which multiple embryos of different quality were transferred and only one of implanted, the higher quality embryo (so-called leading embryo) had the highest probability of implantation.

In our analysis we made a distinction between premenstrual pregnancy loss (loss of conceptus prior to the first measurement of βhCG level 14 days after ovulation or embryo transfer), biochemical pregnancy (loss of conceptus after the first measurement of βhCG level but before the ultrasound (US) confirmation of implantation) and early clinical miscarriage (pregnancy loss after US confirmation of viable pregnancy but before the beginning of the second trimester) (Došen et al., 2011). Biochemical pregnancies and early clinical miscarriages are commonly identified together as early pregnancy losses (EPL).

Basic demographic and clinical characteristics are presented as mean ± standard deviation (SD) or median with 1st and 3rd quartile and analyzed by independent-samples t-test if normally distributed or by Mann-Whitney test if skewed. Categorical data are expressed as proportions and analyzed by chi-squared test. The results are presented as odds ratios and their 95% confidence intervals (CI). P value of under 0.05 was considered to be statistically significant. Statistical analysis was performed using STATISTICA® software, version 8.0 (StatSoft Inc., OK, USA).

#### **2.3.2 Results**

#### **2.3.2.1 Differences in embryo quality indicators and other parameters between the groups**

Average age of the patients was 32 years (in the group of women with endometriosis 32.6 ± 3.5, the youngest patient was 25 and the oldest 42 years old; in the group with tubal infertility 32.5 ± 3.9, the youngest patient was 22 and the oldest 43 years old).

Analysis of differences in quality score of transferred blastocysts between patients with endometriosis and tubal factor infertility showed marginal statistical significance, if all the scores (B1-B8) were analyzed together (chi-square=14.03, p=0.051). Further analysis was

is a modification of the earlier, well established blastocyst evaluation system (Gardner & Schoolcraft, 1999). The classification used in our laboratory takes into consideration four parameters: blastocoel expansion, inner cellular mass (ICM) form, morphology and cohesion of the trophoectoderm (TE) as well as the degree of embryo fragmentation. There are 8 grades of quality of blastocysts (B1 to B8) in this system, with B1 being the best quality score and B8 the worst. The data on blastocyst quality expressed in this way had to be transformed before entering the statistical model. The transformation was performed in two steps. First, the blastocysts from B1 category were designated as optimal quality blastocysts, while those in categories B2–B8 were classified as being of suboptimal (non-optimal) quality. In the second step, in cases where blastocysts of different quality were transferred, the subgroup with blastocysts of different quality was merged with the subgroup in which all transferred blastocysts were of optimal quality. In this way, for the final statistical analyses we had a subgroup with blastocysts of suboptimal quality only and a subgroup with at least one blastocyst of optimal quality. All other possibilities for regrouping were also tested, but it was concluded that the chosen transformation of data showed the best fit with this model. This conclusion was expected, because it was in line with the assumption that in those cases in which multiple embryos of different quality were transferred and only one of implanted, the higher quality embryo (so-called leading embryo) had the highest probability of

In our analysis we made a distinction between premenstrual pregnancy loss (loss of conceptus prior to the first measurement of βhCG level 14 days after ovulation or embryo transfer), biochemical pregnancy (loss of conceptus after the first measurement of βhCG level but before the ultrasound (US) confirmation of implantation) and early clinical miscarriage (pregnancy loss after US confirmation of viable pregnancy but before the beginning of the second trimester) (Došen et al., 2011). Biochemical pregnancies and early clinical miscarriages are commonly identified together as early pregnancy losses (EPL).

Basic demographic and clinical characteristics are presented as mean ± standard deviation (SD) or median with 1st and 3rd quartile and analyzed by independent-samples t-test if normally distributed or by Mann-Whitney test if skewed. Categorical data are expressed as proportions and analyzed by chi-squared test. The results are presented as odds ratios and their 95% confidence intervals (CI). P value of under 0.05 was considered to be statistically significant. Statistical analysis was performed using STATISTICA® software, version 8.0

**2.3.2.1 Differences in embryo quality indicators and other parameters between the groups**  Average age of the patients was 32 years (in the group of women with endometriosis 32.6 ± 3.5, the youngest patient was 25 and the oldest 42 years old; in the group with tubal

Analysis of differences in quality score of transferred blastocysts between patients with endometriosis and tubal factor infertility showed marginal statistical significance, if all the scores (B1-B8) were analyzed together (chi-square=14.03, p=0.051). Further analysis was

infertility 32.5 ± 3.9, the youngest patient was 22 and the oldest 43 years old).

implantation.

(StatSoft Inc., OK, USA).

**2.3.2 Results** 


undertaken to identify the subgroups of the same blastocyst quality score in which possible significant difference was present. The results are presented in Table 1.

Table 1. Comparison of embryo quality scores between the studied groups

Since a significant difference was present only in the subgroups of transferred blastocysts of very low quality (scores B6 and B7), this finding doesn't provide any further insight into the problem.

Analysis of indirect embryo quality indicators showed no statistically significant differences between the groups. The results are presented in Table 2.


a Data are expressed as mean ± standard error.

Table 2. Comparison of indirect indicators of embryo quality between the studied groups.

Analysis of outcomes of IVF-ET cycles also failed to show any statistically significant differences between the groups. Results are presented in Table 3.


\*Biochemical pregnancies and clinical miscarriages combined

Table 3. Comparison of IVF-ET cycles outcomes between the studied groups

In the additional analysis of some of the other important parameters, no significant differences were noted between the groups.

Embryo Quality and Pregnancy Outcome in Infertile Patients with Endometriosis 393

analysis. The impact of possible predictors on the number of live born infants was evaluated using analysis of variance or chi-squared test, as appropriate. For post-hoc comparison of continuous variables, Bonferroni correction of alpha was used, while Keppel modification of

Because of the low number of events per variables (EPV) for early clinical miscarriages, biochemical pregnancies and EPLs included in the logistic regression (Vittinghoff & McCulloch, 2007), a multiple model for analyzing the relative contribution of each predictor was constructed only for these three outcomes: **positive** βhCG 14 days following embryo

After testing all parameters for multicolinearity, a problem was detected in these pairs of variables: the number of retrieved oocytes/the number of fertilized oocytes, the number of retrieved oocytes/the number of embryos on Day 2, the number of fertilized oocytes/the number of embryos on Day 2 and the number of blastocysts/the number of frozen blastocysts. Accordingly, these pairs of variables were not included in the multiple

A univariate logistic regression model suggested a statistically significant correlation between the positive βhCG 14 days after ET and these indirect indicators of embryo quality: the number of embryos on Day 2 (OR=1.091; 95% CI 1.004 - 1.185, P<0.039), the number of blastocysts (OR=1.303; 95% CI 1.138 - 1.491, P<0.001), the number of frozen blastocysts (OR=1.436; 95% CI 1.208 - 1.708, P<0.001) and the embryo quality score of transferred blastocyst (in the form of two subgroups: the one with blastocysts of suboptimal quality only and the other with at least one blastocyst of optimal quality) (OR=5.339; 95% CI 2.782 - 10.246, P<0.001). A statistically significant correlation in univariate model was also noted for the age of the woman (OR=0.857; 95% CI 0.781 - 0.940, P=0.001), the number of retrieved oocytes (OR=1.069; 95% CI 1.006 - 1.135, P=0.030) and the number of fertilized oocytes

After controlling for the all other independent possible predictors in the multiple logistic regression model, the predictors of positive βhCG 14 days after ET in patients with endometriosis identified as statistically significant were the embryo quality score of transferred blastocyst (OR=4.278; 95% CI 1.976 - 9.265, P<0.001) and the age of the woman

Application of a logistic regression in univariate model showed that there was a statistically significant correlation between the clinical pregnancy rate and these indirect measures of embryo quality: the number of blastocysts (OR=1.278; 95% CI 1.122 - 1.457, P<0.001), the number of frozen blastocysts (OR=1.376; 95% CI 1.170 - 1.618, P<0.001) and the embryo quality score of transferred blastocyst (in the form of two subgroups: the one with blastocysts of suboptimal quality only and the other with at least one blastocyst of optimal quality) (OR=4.708; 95% CI 2.466 - 8.986, P<0.001). A statistically significant correlation in univariate model was also noted for the age of the woman (OR=0.875; 95% CI 0.781 - 0.941, P=0.001) and the number of retrieved oocytes (OR=1.069; 95% CI 1.007 - 1.134, P=0.027).

Bonferroni correction was used for categorical variables.

transfer, clinical pregnancy rate and live births rate.

(OR=1.088; 95% CI 1.003 - 1.180, P=0.041).

(OR=0.848; 95% CI 0.757 - 0.950, P=0.005).

**2.3.2.2.2** *Clinical pregnancy rate* 

regression model.

**2.3.2.2.1** *Positive βhCG*


Table 4. Comparison of variables of IVF-ET cycles between the studied groups

#### **2.3.2.2 Blastocyst quality and other possible predictors of various outcomes**

The other objective of our investigation was to define the influence of blastocyst quality on various outcomes of IVF-ET cycles against all other important variables as controls in the group of women with endometriosis.

In our analysis, we incorporated 11 parameters as possible predictors of four main outcomes of stimulated IVF-ET cycles. The encompassed parameters were:


Several examined predictors were transformed in categorical variables, as will be explained below. The six observed outcomes were:


The relationship between continuous predictors and the number of implanted blastocysts was analyzed using Spearman correlation, while the effect of categorical predictors on the number of implanted blastocysts was tested by Mann-Whitney test or Kruskal-Wallis oneway analysis of variance. For all other outcome variables, the effect of possible predictors was analyzed using univariate logistic regression model. Before the incorporation of possible predictors in the multiple regression model, correlations among variables were tested to detect possible multicolinearity and to choose appropriate variables for the final analysis. The impact of possible predictors on the number of live born infants was evaluated using analysis of variance or chi-squared test, as appropriate. For post-hoc comparison of continuous variables, Bonferroni correction of alpha was used, while Keppel modification of Bonferroni correction was used for categorical variables.

Because of the low number of events per variables (EPV) for early clinical miscarriages, biochemical pregnancies and EPLs included in the logistic regression (Vittinghoff & McCulloch, 2007), a multiple model for analyzing the relative contribution of each predictor was constructed only for these three outcomes: **positive** βhCG 14 days following embryo transfer, clinical pregnancy rate and live births rate.

After testing all parameters for multicolinearity, a problem was detected in these pairs of variables: the number of retrieved oocytes/the number of fertilized oocytes, the number of retrieved oocytes/the number of embryos on Day 2, the number of fertilized oocytes/the number of embryos on Day 2 and the number of blastocysts/the number of frozen blastocysts. Accordingly, these pairs of variables were not included in the multiple regression model.

#### **2.3.2.2.1** *Positive βhCG*

392 Endometriosis - Basic Concepts and Current Research Trends

**Tubal factor group (N=173)** 

**P value** 

**(N=173)** 

Table 4. Comparison of variables of IVF-ET cycles between the studied groups

**2.3.2.2 Blastocyst quality and other possible predictors of various outcomes** 

of stimulated IVF-ET cycles. The encompassed parameters were:

(HMG) or recombinant follicle stimulation hormone (FSH)),

No. of oocytes retrieved (N) 11.2 ± 0.41 11.1 ± 0.39 0.773 No. of fertilized oocytes (N) 7.6 ± 0.31 7.5 ± 0.29 0.859 Fertilization rate (%) 69.4 ± 1.39 69.0 ± 1.38 0.847 Male factor present (%) 96 (55.5) 84 (48.6) 0.197

The other objective of our investigation was to define the influence of blastocyst quality on various outcomes of IVF-ET cycles against all other important variables as controls in the

In our analysis, we incorporated 11 parameters as possible predictors of four main outcomes

• type of gonadotrophin used for stimulation (human menopausal gonadotrophin

Several examined predictors were transformed in categorical variables, as will be explained

• early pregnancy loss rate (EPL - biochemical pregnancies and early clinical miscarriages

The relationship between continuous predictors and the number of implanted blastocysts was analyzed using Spearman correlation, while the effect of categorical predictors on the number of implanted blastocysts was tested by Mann-Whitney test or Kruskal-Wallis oneway analysis of variance. For all other outcome variables, the effect of possible predictors was analyzed using univariate logistic regression model. Before the incorporation of possible predictors in the multiple regression model, correlations among variables were tested to detect possible multicolinearity and to choose appropriate variables for the final

**Variable Endometriosis group** 

group of women with endometriosis.

• fertilization method (IVF or ICSI),

• number of retrieved oocytes, • number of fertilized oocytes,

• number of embryos on Day 2,

• number of transferred blastocysts, • number of frozen blastocysts and

below. The six observed outcomes were:

• positive βhCG 14 days after ET,

• biochemical pregnancy rate, • early clinical miscarriage rate, and

• clinical pregnancy rate,

taken together).

• live births rate,

• number of blastocysts (embryos on Day 5),

• embryo quality score of transferred blastocysts.

• patient's age,

• fertilization rate,

A univariate logistic regression model suggested a statistically significant correlation between the positive βhCG 14 days after ET and these indirect indicators of embryo quality: the number of embryos on Day 2 (OR=1.091; 95% CI 1.004 - 1.185, P<0.039), the number of blastocysts (OR=1.303; 95% CI 1.138 - 1.491, P<0.001), the number of frozen blastocysts (OR=1.436; 95% CI 1.208 - 1.708, P<0.001) and the embryo quality score of transferred blastocyst (in the form of two subgroups: the one with blastocysts of suboptimal quality only and the other with at least one blastocyst of optimal quality) (OR=5.339; 95% CI 2.782 - 10.246, P<0.001). A statistically significant correlation in univariate model was also noted for the age of the woman (OR=0.857; 95% CI 0.781 - 0.940, P=0.001), the number of retrieved oocytes (OR=1.069; 95% CI 1.006 - 1.135, P=0.030) and the number of fertilized oocytes (OR=1.088; 95% CI 1.003 - 1.180, P=0.041).

After controlling for the all other independent possible predictors in the multiple logistic regression model, the predictors of positive βhCG 14 days after ET in patients with endometriosis identified as statistically significant were the embryo quality score of transferred blastocyst (OR=4.278; 95% CI 1.976 - 9.265, P<0.001) and the age of the woman (OR=0.848; 95% CI 0.757 - 0.950, P=0.005).

#### **2.3.2.2.2** *Clinical pregnancy rate*

Application of a logistic regression in univariate model showed that there was a statistically significant correlation between the clinical pregnancy rate and these indirect measures of embryo quality: the number of blastocysts (OR=1.278; 95% CI 1.122 - 1.457, P<0.001), the number of frozen blastocysts (OR=1.376; 95% CI 1.170 - 1.618, P<0.001) and the embryo quality score of transferred blastocyst (in the form of two subgroups: the one with blastocysts of suboptimal quality only and the other with at least one blastocyst of optimal quality) (OR=4.708; 95% CI 2.466 - 8.986, P<0.001). A statistically significant correlation in univariate model was also noted for the age of the woman (OR=0.875; 95% CI 0.781 - 0.941, P=0.001) and the number of retrieved oocytes (OR=1.069; 95% CI 1.007 - 1.134, P=0.027).

Embryo Quality and Pregnancy Outcome in Infertile Patients with Endometriosis 395

In the further analysis of our data, we also showed that in infertile patients suffering only from endometriosis, embryo quality was a statistically significant positive predictor of positive βhCG measurement (if embryo quality was expressed in the form of embryo quality score, OR=4.278; 95% CI 1.976 - 9.265, P<0.001), clinical pregnancy rate (if embryo quality was expressed in the form of embryo quality score, OR=3.485; 95% CI 1.608 - 7.553, P=0.002) and live births rate (if embryo quality was expressed in the form of number of frozen blastocysts, OR=1.319; 95% CI 1.034 - 1.683, P=0.026). As expected, the patient's age was a statistically significant negative predictor of the success of IVF-ET cycles (positive βhCG measurement, clinical pregnancy rate and live births rate) in the observed group of

Endometriosis is still an insufficiently explained condition. Numerous controversies still surrounding this complex disease indicate an obvious need for further clinical studies, metaanalyses and explanation of its pathophysiologic mechanisms. Should a consensus be reached on a precise methodology, future studies would definitely be more informative and

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Barragán, JC.; Brotons, J.; Ruiz, JA. & Acien, P. (1992). Experimentally induced

Brizek, CL.; Schlaff, S.; Pellegrini, VA.; Frank, JB. & Worrilow, KC. (1995). Increased

Croxato, HB.; Ortiz, ME.; Guiloff, E.; Ibarra, A.; Salvatierra, AM.; Croxatto, HD. & Spilman,

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patients.

**4. References** 

results easier to use in clinical practice.

After controlling for all other independent possible predictors in the multiple logistic regression model, the predictors of the clinical pregnancy rate in patients with endometriosis identified as statistically significant were the embryo quality score (OR=3.485; 95% CI 1.608 - 7.553, P=0.002) and the age of the woman (OR=0.861; 95% CI 0.770 - 0.963, P=0.009).

#### **2.3.2.2.3** *Live births*

A univariate logistic regression model indicated that there was a statistically significant correlation between the live births rate and these indirect measures of embryo quality: the number of blastocysts (OR=1.313; 95% CI 1.139 - 1.513, P<0.001), the number of frozen blastocysts (OR=1.402; 95% CI 1.183 - 1.661, P<0.001) and the embryo quality score of transferred blastocyst (in the form of two subgroups: the one with blastocysts of suboptimal quality only and the other with at least one blastocyst of optimal quality) (OR=3.316; 95% CI 1.693 - 6.496, P<0.001). A statistically significant correlation in univariate model was also noted for the age of the woman (OR=0.861; 95% CI 0.780 - 0.950, P=0.03).

After controlling for all other independent possible predictors in the multiple logistic regression model, the predictors of the live births rate in patients with endometriosis identified as statistically significant were the age of the woman (OR=0.851; 95% CI 0.756 - 0.958, P=0.07) and the number of frozen blastocysts (OR=1.319; 95% CI 1.034 - 1.683, P=0.026).
