Intrauterine insemination of cultured peripheral blood mononuclear cells prior to embryo transfer improves clinical outcome for patients with repeated implantation failures

Madkour, Aicha; Bouamoud, Nouzha; Louanjli, Noureddine; Kaarouch, Ismail; Copin, Henri; Benkhalifa, Moncef; Sefrioui, O

doi:10.1017/s0967199414000719

Cited by 60 publications

(71 citation statements)

References 70 publications

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“…However, this result could be explained by a possible presence of embryonic aneuploidies [14, 16, 18, 25, 34, 35] issued from oocytes with CLCG which are responsible for implantation failures before clinical pregnancy. There is probable involvement of other intra-uterine dysregulating factors [28] which are associated with oocyte dysmorphism [11, 13, 35]. …”

Section: Discussionmentioning

confidence: 99%

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Impact of oocytes with CLCG on ICSI outcomes and their potential relation to pesticide exposure

et al. 2017

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BackgroundOocyte quality is a key limiting factor in female fertility which is primarily reflected in morphological features. Centrally located cytoplasm granulation (CLCG) is one type of cytoplasmic dimorphism exhibited by oocytes that could be linked to pesticide exposure with a significant risk of decreased ICSI outcomes.MethodsThis retrospective study included 633 women who were part of an intracytoplasmic spermatozoa injection (ICSI) program between 2009 and 2011. The participants lived in the Picardy region of France and had been exposed to pesticides. The participants were divided in two groups based on prevalence of oocytes with CLCG (LCLCG [n = 83]: low prevalence of oocytes with CLCG under 25%. HCLCG [n = 68]: high prevalence of CLCG over 75%). The embryological and clinical outcomes were analysed for both groups and were calculated using the difference between the two values.ResultsResults for couples with HCLCG compared to LCLCG showed a decrease in embryo cleavage, ongoing pregnancy, and live birth rates (82%, 14%, 13% vs 99%, 32%, 30%, respectively).The early miscarriage rate was increased (47% vs 11%), with an OR of 3.1 (95%CI [2.1–4.1]). Due to high pesticide exposure (over 3000 g/ha), there is a higher risk of a resulting disturbed oocyte cohort with a high prevalence of CLCG over 75%.ConclusionThe high prevalence of oocytes with CLCG over 75% has a negative effect on embryos and the general ICSI clinical outcomes. Furthermore, a putative association between pesticide exposure and risk of CLCG was identified, justifying the need for further research and a potential need to find alternative assisted reproductive technologies for these couples.Trial registrationTabacfertimasc. ID number: ID2011-A00634–37; registered 2011/2/8

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Section: Discussionmentioning

confidence: 99%

“…The resulting embryos were cultured up to day 3 [28]. Adequate embryo quality (good quality embryos; A + B) was defined based on the presence of uniform size and shape of blastomeres and fragmentation lower or equal to 10% [25].…”

Section: Methodsmentioning

confidence: 99%

Impact of oocytes with CLCG on ICSI outcomes and their potential relation to pesticide exposure

et al. 2017

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“…Indeed, we included couples with unexplained male infertility and previous IVF failures. All women received the same antagonist ovarian stimulation protocol (Madkour et al, ) to minimize the effect of other parameters. Men (24 to 56‐year‐old) were divided in two age groups, considering the age of 40 years as cutoff: APA group ( n = 41; ≥40 years) and young (Y) group ( n = 42; <40 years).…”

Section: Methodsmentioning

confidence: 99%

Paternal age: Negative impact on sperm genome decays and IVF outcomes after 40 years

Kaarouch

Bouamoud

Madkour

et al. 2018

Molecular Reproduction Devel

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This study assessed sperm quality declining on relation to paternal age and its impact on in vitro fertilization (IVF) outcomes in order to estimate the APA (Advanced Paternal Age) cutoff. For this, 83 couples undergoing IVF treatment for male factor infertility were enrolled. The women age was ≤39 years, whereas the men were divided in two groups: APA (n = 41; age ≥ 40 years) and young (Y) (n = 42; age < 40 years). Conventional semen parameters (volume, concentration, motility, vitality, and morphology) were analyzed in the collected sperm samples. Furthermore, sperm genome decays (SGD) was assessed by TUNEL assay (DNA fragmentation), aniline blue staining (chromatin decondensation), and fluorescent in situ hybridization (aneuploidy). No significant difference was found concerning the conventional semen parameters between APA and Y groups. Conversely, SGD analysis showed increased DNA fragmentation; chromatin decondensation and sperm aneuploidy rates in the APA group (respectively, 41%, 43%, and 14% vs. 25%, 23%, and 4% in Y group). IVF outcomes also were affected by paternal age as indicated by the rates of cancelled embryo transfers, clinical pregnancy and miscarriage in the two groups APA and Y (29%, 17%, and 60% vs. 10%, 32%, and 42%). Finally, statistical analysis of the results suggests that the age of 40 should be considered as the APA cutoff during ART attempts.

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“…Moreover, approximately 10% of patients have unexplained recurrent implantation failure (RIF) after several IVF treatments [1]. At present, RIF caused by various etiological factors remains a challenge for fertility clinicians using assisted reproductive technology (ART) worldwide [2].…”

Section: Introductionmentioning

confidence: 99%

Increased Krüppel-like factor 12 in recurrent implantation failure impairs endometrial decidualization by repressing Nur77 expression

Huang

Zhou

Yan

et al. 2017

Reprod Biol Endocrinol

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BackgroundDecidualization is a prerequisite for successful implantation and the establishment of pregnancy. A critical role of impaired decidualization in subfertility has been established. In human endometrial stromal cells (hESCs), Krüppel-like factor 12 (KLF12) and Nur77 are novel regulators of decidualization. We investigated whether KLF12 impaired the decidualization of hESCs in recurrent implantation failure (RIF) patients.MethodsEndometrial tissues and hESCs were collected from RIF patients (n = 34) and fertile controls (n = 30) for in vitro analysis. Primary hESCs isolated from RIF endometrial tissues were used to evaluate the biological functions of KLF12 and Nur77. In addition, their molecular mechanisms were investigated by adenovirus-mediated overexpression. Gene expression regulation was examined by real-time-quantitative PCR (qRT-PCR), immunostaining and luciferase reporter assay. Further, blastocyst-like spheroid (BLS) and blastocyst implantation models were performed to examine the roles of KLF12 and Nur77 during embryo expansion on hESCs.ResultshESCs from the RIF patients showed a poor decidual response, mainly characterized by decreased decidual prolactin (dPRL) secretion, impaired transformation and limited BLS expansion. In addition, KLF12 expression was increased in endometrial tissues from the RIF patients compared with those from the fertile controls, especially in stromal compartments. The opposite results were observed for Nur77 expression in these tissues. KLF12 repressed hESC decidualization by decreasing Nur77 expression. Mechanistically, KLF12 bound to a conserved site in the Nur77 promoter region. Nur77 overexpression significantly reversed the KLF12-mediated repression of dPRL expression, decidual transformation and BLS/blastocyst expansion.ConclusionsKLF12 impairs endometrial decidualization by transcriptionally repressing Nur77, and Nur77 overexpression reverses the poor decidual response of hESCs in RIF patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12958-017-0243-8) contains supplementary material, which is available to authorized users.

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Intrauterine insemination of cultured peripheral blood mononuclear cells prior to embryo transfer improves clinical outcome for patients with repeated implantation failures

Cited by 60 publications

References 70 publications

Impact of oocytes with CLCG on ICSI outcomes and their potential relation to pesticide exposure

Impact of oocytes with CLCG on ICSI outcomes and their potential relation to pesticide exposure

Paternal age: Negative impact on sperm genome decays and IVF outcomes after 40 years

Increased Krüppel-like factor 12 in recurrent implantation failure impairs endometrial decidualization by repressing Nur77 expression

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