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Endometriosis, Ovarian Reserve and Live Birth Rate Following in Vitro THIEME 218 Original Article Endometriosis, Ovarian Reserve and Live Birth Rate Following In Vitro Fertilization/ Intracytoplasmic Sperm Injection Endometriose, reserva ovariana e taxa de nascidos vivos após FIV/ICSI Marcela Alencar Coelho Neto1 Wellington de Paula Martins1 Caroline Mantovani da Luz1 Bruna Talita Gazeto Melo Jianini1 Rui Alberto Ferriani1 Paula Andrea Navarro1 1 Department of Obstetrics and Gynecology, Faculdade de Medicina Address for correspondence Paula Andrea Navarro, MD, PhD, de Ribeirão Preto, Universidade de São Paulo – USP, Ribeirão Preto, Departmento de Ginecologia e Obstetrícia, Faculdade de Medicina de SP, Brasil Ribeirão Preto, Hospital das Clínicas de Ribeirão Preto, Centro de Reprodução Humana, Universidade de São Paulo, Avenida Rev Bras Ginecol Obstet 2016;38:218–224. Bandeirantes, 3.900, 8o andar, Ribeirão Preto, caixa postal: 14048- 900, Ribeirão Preto, SP, Brazil (e-mail: [email protected]). Abstract Purpose To evaluate whether women with endometriosis have different ovarian reserves and reproductive outcomes when compared with women without this diagnosis undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ ICSI), and to compare the reproductive outcomes between women with and without the diagnosis considering the ovarian reserve assessed by antral follicle count (AFC). Methods This retrospective cohort study evaluated all women who underwent IVF/ ICSI in a university hospital in Brazil between January 2011 and December 2012. All patients were followed up until a negative pregnancy test or until the end of the pregnancy. The primary outcomes assessed were number of retrieved oocytes and live birth. Women were divided into two groups according to the diagnosis of endometri- osis, and each group was divided again into a group that had AFC 6 (poor ovarian reserve) and another that had AFC 7 (normal ovarian reserve). Continuous variables with normal distribution were compared using unpaired t-test, and those without normal distribution, using Mann-Whitney test. Binary data were compared using either Fisher’s exact test or Chi-square (2)test.Thesignificance level was set as p < 0.05. Results 787 women underwent IVF/ICSI (241 of which had endometriosis). Although the mean age has been similar between women with and without the diagnosis of Keywords endometriosis (33.8 Æ 4 versus 33.7 Æ 4.4years,respectively),poorovarianreserves ► endometriosis were much more common in women with endometriosis (39.8 versus 22.7%). The ► ovarian reserve chance of achieving live birth was similar between women with the diagnosis of ► assisted reproduction endometriosis and those without it (19.1 versus 22.5%), and also when considering ► IVF only women with a poor ovarian reserve (9.4 versus 8.9%) and only those with a normal ► ICSI ovarian reserve (25.5 versus 26.5%). received DOI http://dx.doi.org/ Copyright © 2016 by Thieme Publicações January 5, 2016 10.1055/s-0036-1584126. Ltda, Rio de Janeiro, Brazil accepted ISSN 0100-7203. March 30, 2016 published online May 19, 2016 Endometriosis, Ovarian Reserve and Live Birth Rate Following IVF\ICSI Coelho Neto et al. 219 Conclusions Women diagnosed with endometriosis are more likely to have a poor ovarian reserve; however, their chance of conceiving by IVF/ICSI is similar to the one observed in patients without endometriosis and with a comparable ovarian reserve. Resumo Objetivo Avaliar se mulheres com endometriose possuem diferenças quanto a reserva ovariana (RO) e a resultados de reprodução assistida quando comparadas a mulheres sem este diagnóstico submetidas IVF/ICSI (in vitro fertilization/intracytoplas- mic sperm injection), e comparar resultados reprodutivos entre mulheres com e sem o diagnóstico, considerando a RO obtida pela contagem de folículos antrais (CFA). Métodos Este estudo de coorte retrospectivo avaliou todas as mulheres submetidas à FIV/ICSI em uma universidade do Brasil nos anos de 2011 e 2012. Todas as pacientes foram seguidas até um teste negativo de gravidez ou até o final da gestação. Os desfechos primários analisados foram o número do oócitos captados e nascidos vivos. As mulheres foram divididas em 2 grupos de acordo com o diagnóstico de endome- triose e subdivididas de acordo com a CFA 6(baixaRO)e 7 (RO normal). As variáveis contínuas com distribuição normal foram comparadas pelo teste t não pareado e sem distribuição normal pelo teste de Mann-Whitney. Os dados binários foramcomparadosporambosostestesQui-quadrado(2)eexatodeFisher.Onívelde significância foi definido como p < 0,05. Resultados 787 mulheres foram submetidas a IVF/ICSI (241 com endometriose). Embora a média de idade tenha sido similar entre as mulheres com e sem o diagnóstico Palavras-chave de endometriose (33,8 Æ 4 versus 33,7 Æ 4.4 anos, respectivamente), a baixa RO é ► endometriose muito mais comum em mulheres com endometriose (39,8 versus 22,7%). A chance de ► reserva ovariana obter um nascido vivo foi similar entre as mulheres com e sem endometriose (19,1 ► reprodução versus 22,5%), e também quando consideradas apenas as mulheres com baixa RO (9,4 assistida versus 8,9%), e apenas com RO normal (25,5 versus 26,5%). ► fertilização in Conclusões Mulheres diagnosticadas com endometriose são mais susceptíveis a ter virto baixa RO; no entanto, suas chances de conceber por IVF/ICSI são similares às ► ICSI observadas em pacientes sem endometriose e com uma RO comparável. Introduction but ART treatments are responsible for the highest success rates.11,12 Subfertility is the inability of achieving a pregnancy after one The relationship between the presence and severity of year of regular, unprotected intercourse.1 Approximately endometriosis and the reproductive outcomes in women – 15% of women in reproductive age are considered subfer- undergoing ART are controversial.13 15 The first meta-analysis – tile.2 4 Assisted Reproduction Technologies (ARTs), particu- evaluating this issue found that endometriosis reduces the larly in vitro fertilization (IVF) and intracytoplasmic sperm chances of achieving pregnancy in IVF/ICSI cycles, and that injection (ICSI), are frequently used to help subfertile couples patients with moderate to severe endometriosis (III/IV) have to conceive. even worse results.14 The second review observed that only Endometriosis is one of the most cited causes of subfer- severe endometriosis impairs implantation and clinical preg- tility, being much more common in subfertile (25–40%) than nancy rates when compared with women without the dis- in fertile woman (0.5–5.0%).5 This disease is defined by the ease.15 However, the latest and largest published review found presence of endometrial tissue outside the uterine cavity, moderate quality evidence suggesting that endometriosis does and the mechanisms through which endometriosis impairs not affect the chance of achieving clinical pregnancy and live fertility are still unclear.6 Pelvic adhesions and distortion of birth when considering only the fresh transfer cycle.13 Fur- pelvic anatomy are associated with subfertility, and are thermore, the same review suggests that patients with endo- frequently observed in moderate and severe cases of endo- metriosis have a reduced ovarian reserve, once fewer oocytes metriosis.7 However, the mechanism underlying minimal or are retrieved from women in this group. Since a poor ovarian mild endometriosis related to subfertility is unclear, and may reserve is associated with poor reproductive outcomes,16,17 it be related to impairment of oocyte development, embryo- is possible that the differences in the ovarian reserve, and not – genesis and implantation.8 10 The ideal fertility treatment endometriosis itself, might be the cause of the heterogeneity for women with endometriosis is not well established yet, observed in the studies published so far.13 Rev Bras Ginecol Obstet Vol. 38 No. 5/2016 220 Endometriosis, Ovarian Reserve and Live Birth Rate Following IVF\ICSI Coelho Neto et al. Thus, the objective of this study was to evaluate whether For a second analysis, women were further stratified into two women with endometriosis have different ovarian reserves subgroups: AFC 6andAFC 7. This latter analysis was and reproductive outcomes when compared with women performed to separate women with expected poor ovarian without this diagnosis undergoing IVF/ICSI. We also com- response according to the AFC cutoff values suggested in the pared the reproductive outcomes between women with and Bologna criteria.24 The study size was determined by the without the diagnosis of endometriosis considering the primary outcome number of oocytes retrieved. Considering a ovarian reserve assessed by antral follicle count (AFC) evalu- difference of one oocyte retrieved as being clinically rele- ated before the beginning of the controlled ovarian stimula- vant,25 a standard deviation (SD) of 4.5 oocytes retrieved at tion (COS) for FIV/ICSI. our service,26 a proportion of women with endometriosis to be close to 30%,13 significance level ¼ p < 0.05, we would Methods need 760 women to have a power of 80% to detect this difference. A mean of 40 women are submitted to treatment This retrospective cohort study included all women who under- cycle per month in our clinic. Considering that part of these went IVF/ICSI at thefertilityclinicof theuniversity hospital of the women repeat the treatment in a short period of time, we Ribeirão Preto Medical School, Universidade de São Paulo, Brazil, calculated that we would need to retrieve data from between January 2011 and December 2012. All data were 24
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