Ovarian Reserve in Young Women of Reproductive Age with Crohnʼs Disease

Fréour, Thomas; Miossec, Charline; Bach-Ngohou, Kalyane; Dejoie, Thomas; Flamant, Mathurin; Maillard, Olivier; Denis, Marc G.; Barrière, P.; Varannes, Stanislas Bruley des; Bourreille, Arnaud; Masson, Damien

doi:10.1002/ibd.21872

Cited by 52 publications

(56 citation statements)

References 42 publications

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“…Elevated levels of TNF-α in the follicular fluid were correlated with poor oocyte quality (44), and Winger et al (45) showed that TNF-α blockage improves IVF outcomes in young infertile women. Recent studies show that patients with endometriosis and Crohn disease have significantly lower AMH levels compared with healthy controls, supporting the hypothesis that uncontrolled inflammation adversely affects the ovarian reserve (27,28). Previous studies suggested that IL-1 hinders hormonal regulation within the ovary (46,47).…”

Section: Discussionmentioning

confidence: 81%

“…In the male, high levels of IL-1 in the testis, as observed in IL-1 receptor antagonistdeficient mice, impair sperm quality and its ability to fertilize oocytes (26). Recent studies suggest that inflammatory conditions may affect ovarian reserve in women (27,28). However, to the best of our knowledge, the possible involvement of inflammatory pathways and the role of IL-1 in the age-related exhaustion of ovarian reserve have never been directly approached.…”

Section: Significancementioning

confidence: 99%

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Interleukin-1 deficiency prolongs ovarian lifespan in mice

Uri-Belapolsky

Shaish

Eliyahu

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Oocyte endowment dwindles away during prepubertal and adult life until menopause occurs, and apoptosis has been identified as a central mechanism responsible for oocyte elimination. A few recent reports suggest that uncontrolled inflammation may adversely affect ovarian reserve. We tested the possible role of the proinflammatory cytokine IL-1 in the age-related exhaustion of ovarian reserve using IL-1α and IL-1β-KO mice. IL-1α-KO mice showed a substantially higher pregnancy rate and litter size compared with WT mice at advanced age. The number of secondary and antral follicles was significantly higher in 2.5-mo-old IL-1α-KO ovaries compared with WT ovaries. Serum anti-Müllerian hormone, a putative marker of ovarian reserve, was markedly higher in IL-1α-KO mice from 2.5 mo onward, along with a greater ovarian response to gonadotropins. IL-1β-KO mice displayed a comparable but more subtle prolongation of ovarian lifespan compared with IL-1α-KO mice. The protein and mRNA of both IL-1α and IL-1β mice were localized within the developing follicles (oocytes and granulosa cells), and their ovarian mRNA levels increased with age. Molecular analysis revealed decreased apoptotic signaling [higher B-cell lymphoma 2 (BCL-2) and lower BCL-2-associated X protein levels], along with a marked attenuation in the expression of genes coding for the proinflammatory cytokines IL-1β, IL-6, and TNF-α in ovaries of IL-1α-KO mice compared with WT mice. Taken together, IL-1 emerges as an important participant in the age-related exhaustion of ovarian reserve in mice, possibly by enhancing the expression of inflammatory genes and promoting apoptotic pathways.

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Section: Discussionmentioning

confidence: 81%

Section: Significancementioning

confidence: 99%

Interleukin-1 deficiency prolongs ovarian lifespan in mice

Uri-Belapolsky

Shaish

Eliyahu

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…When oocytes are exposed to an aged ovarian microenvironment, they themselves will undergo a process of reproductive aging (Tatone et al ., ). Inflammatory cytokines constitute one of the most potent factors in the ovarian microenvironment that are involved in physiologic and pathologic processes within the ovary (Boots & Jungheim, ), and recent studies have shown effects of inflammatory conditions on ovarian reserve in women (Freour et al ., ). Elevated levels of pro‐inflammatory factors, including IL‐1β and TNF‐α (tumor necrosis factor‐a), have been reported to be associated with poor oocyte quality and negative effects on IVF outcomes (Lee et al ., ; Revelli et al ., ; Winger et al ., ).…”

Section: Discussionmentioning

confidence: 97%

Short‐term rapamycin treatment increases ovarian lifespan in young and middle‐aged female mice

et al. 2017

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SummaryAlthough age‐related ovarian failure in female mammals cannot be reversed, recent strategies have focused on improving reproductive capacity with age, and rapamycin is one such intervention that has shown a potential for preserving the ovarian follicle pool and preventing premature ovarian failure. However, the application is limited because of its detrimental effects on follicular development and ovulation during long‐term treatment. Herein, we shortened the rapamycin administration to 2 weeks and applied the protocol to both young (8 weeks) and middle‐aged (8 months) mouse models. Results showed disturbances in ovarian function during and shortly after treatment; however, all the treated animals returned to normal fertility 2 months later. Following natural mating, we observed prolongation of ovarian lifespan in both mouse models, with the most prominent effect occurring in mice older than 12 months. The effects of transient rapamycin treatment on ovarian lifespan were reflected in the preservation of primordial follicles, increases in oocyte quality, and improvement in the ovarian microenvironment. These data indicate that short‐term rapamycin treatment exhibits persistent effects on prolonging ovarian lifespan no matter the age at initiation of treatment. In order not to disturb fertility in young adults, investigators should in the future consider applying the protocol later in life so as to delay menopause in women, and at the same time increase ovarian lifespan.

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“…Former studies have found a considerable reduction in postoperative fertility in women with UC requiring ileoanal pouch anastomosis (IPAA),9–12 and after CD surgery 13 14. Excluding voluntary childlessness, additional causes of infertility may include increased disease activity and low ovarian reserve 13 15 16. Serum anti-Mullerian hormone, an indicator of ovarian reserve, is lower in women with CD, especially during periods of active disease, compared with healthy controls 15 16…”

Section: Introductionmentioning

confidence: 99%

Live birth and adverse birth outcomes in women with ulcerative colitis and Crohn's disease receiving assisted reproduction: a 20-year nationwide cohort study

Nørgård

Fedder

Silva

et al. 2016

Gut

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Objective To examine the chance of live births and adverse birth outcomes in women with ulcerative colitis (UC) and Crohn's disease (CD) compared with women without inflammatory bowel disease (IBD) who have undergone assisted reproductive technology (ART) treatments. Methods This was a nationwide cohort study based on Danish health registries, comprising all women with an embryo transfer during 1 January 1994 through 2013. The cohorts comprised 1360 ART treatments in 432 women with UC, 554 ART treatments in 182 women with CD and 148 540 treatments in 52 489 women without IBD. Our primary outcome was live births per ART treatment cycle. We controlled for multiple covariates in the analyses. Our secondary outcomes were adverse birth outcomes. Results The chance of a live birth for each embryo transfer was significantly reduced in ART treatments in women with UC (OR=0.73, 95% CI 0.58 to 0.92), but not significantly reduced in the full model of ART treatments in women with CD (OR=0.77, 95% CI 0.52 to 1.14). Surgery for CD before ART treatment significantly reduced the chance of live birth for each embryo transfer (OR=0.51, 95% CI 0.29 to 0.91). In children conceived through ART treatment by women with UC, the OR of preterm birth was 5.29 (95% CI 2.41 to 11.63) in analyses including singletons and multiple births; restricted to singletons the OR was 1.80, 95% CI 0.49 to 6.62. Conclusions Our results suggest that women with UC and CD receiving ART treatments cannot expect the same success for each embryo transfer as other infertile women. Women with CD may seek to initiate ART treatment before needing CD surgery. Increased prenatal observation in UC pregnancies after ART should be considered.

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Ovarian Reserve in Young Women of Reproductive Age with Crohnʼs Disease

Cited by 52 publications

References 42 publications

Interleukin-1 deficiency prolongs ovarian lifespan in mice

Interleukin-1 deficiency prolongs ovarian lifespan in mice

Short‐term rapamycin treatment increases ovarian lifespan in young and middle‐aged female mice

Live birth and adverse birth outcomes in women with ulcerative colitis and Crohn's disease receiving assisted reproduction: a 20-year nationwide cohort study

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