Evaluating the role of paternal factors in aetiology and prognosis of recurrent pregnancy loss: study protocol for a hospital-based multicentre case–control study and cohort study (REMI III project)

IntroductionRecurrent pregnancy loss (RPL) is defined as the spontaneous demise of two or more pregnancies before the fetus reaches viability. Despite investigation of multiple known maternal risk factors, in more than 50% of couples, this condition remains unexplained. Studies focusing on paternal factors in RPL are scarce, and therefore, paternal evaluation in RPL is currently very limited. However, regarding single miscarriage, there are multiple publications suggesting a contributive role of paternal factors. In this project, we aim to identify paternal factors associated with RPL and to improve couple-specific prediction of future pregnancy outcomes by developing a prediction model containing both maternal and paternal factors.Methods and analysisIn a case–control design, the relation between unexplained RPL and paternal age, lifestyle factors, sperm DNA damage and immunomodulatory factors in peripheral blood and semen will be studied. Prospectively, 135 couples with naturally conceived unexplained RPL (cases) and 135 fertile couples without a history of pregnancy loss (controls) will be included, with collection of paternal blood and semen samples and documentation of clinical and lifestyle characteristics. In addition, 600 couples from both groups will be included retrospectively. To adjust for confounders, multivariate logistic regression will be used. The predictive value of paternal and maternal factors will be studied in the total RPL cohort consisting of approximately 735 couples. The primary outcome of the cohort study is live birth within 5 years after initial visit of the clinic. Secondary outcomes are ongoing pregnancy, time interval until next pregnancy and pregnancy complications.Ethics and disseminationThis project is approved by the Medical Research Ethics Committee of the Leiden University Medical Center. No risks or burden are expected from the study. The findings of this study will be disseminated via peer-reviewed publications and presentations at international conferences.Trial registration numberNL7762

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Proteomic Signatures in Spermatozoa Reveal the Role of Paternal Factors in Recurrent Pregnancy Loss

The World Journal of Men s Health ◽

10.5534/wjmh.190034 ◽

2020 ◽

Vol 38 (1) ◽

pp. 103 ◽

Cited By ~ 3

Author(s):

Gayatri Mohanty ◽

Soumya Ranjan Jena ◽

Jasmine Nayak ◽

Sujata Kar ◽

Luna Samanta

Keyword(s):

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Paternal Factors

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The role of neopterin and anti-Mullerian hormone in unexplained recurrent pregnancy loss – a case-control study

Journal of Obstetrics and Gynaecology ◽

10.1080/01443615.2019.1586850 ◽

2019 ◽

Vol 39 (7) ◽

pp. 996-999

Author(s):

Halime Sencan ◽

Nadi Keskin ◽

Ghanim Khatib

Keyword(s):

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Case Control Study ◽

Case Control ◽

Control Study

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Consistent Role of Insulin Resistance in Recurrent Pregnancy Loss and Recurrent Implantation Failure: A Case-control Study

10.21203/rs.3.rs-827067/v1 ◽

2021 ◽

Author(s):

Miao Ding ◽

Fengyi He ◽

Xiaojia Li ◽

Sushi Jiang ◽

Yacong Cao ◽

...

Keyword(s):

Insulin Resistance ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Case Control Study ◽

Case Control ◽

Model Assessment ◽

Implantation Failure ◽

Recurrent Implantation Failure ◽

Control Study

Abstract Background: To explore the role of insulin resistance (IR) in patients with recurrent pregnancy loss (RPL) and/or recurrent implantation failure (RIF) treated with assisted reproductive technology (ART).Methods: We conducted a case-control study in a tertiary hospital from 2012 to 2018, We included 212 cases of simple RPL (only involved in RPL), 123 cases of simple RIF (only involved in RIF), 67 cases involved in both conditions (complicated group). We screened 123 women as the control cohort, who underwent ART due to male infertile, with no adverse pregnant outcomes. We examined the plasm glucose and insulin level in both fasting and postprandial condition after the oral glucose tolerance test (OGTT) and calculated the area under the curve of glucose (AUGG) and insulin (AUCI) as well as the homeostasis model assessment for insulin resistance and β-cell function (HOMA-IR and HOMA-β).Results: Both the simple RPL group and the complicated group had significantly higher fasting insulin (FINS), HOMA-IR and HOMA-β than the control group. The simple RIF group had the lowest level of FINS, HOMA-IR and HOMA-β. The incidences of IR were significantly higher in both the simple RPL group and the complicated group than the other two groups. After adjusted for age and waist-hip ratio (WHR), the simple RIF group had the highest fasting plasma glucose (FPG) [adjusted-mean (95%CI), 5.20 (5.09-5.33) mmol/L] and lower FINS [adjusted-mean (95%CI), 10.77 (9.25-12.29) mU/L] and HOMA-β [adjusted-mean (95%CI), 127.76 (83.56-171.97)]; the simple RPL group had the highest FINS [adjusted-mean (95%CI), 12.09 (11.21-12.98) mU/L] and HOMA-β [adjusted-mean (95%CI), 189.74 (164.29-215.18)] and a lower FPG [adjusted-mean (95%CI), 5.03 (4.97-5.10) mmol/L]. The FINS tended to increase with times of implantation failure among those patients with implantation failure fewer than six times. However, patients with more than six times implantation failure had extremely low FINS when compared with those with a history of five or six times (P<0.05). Conclusion: In patients undergoing ART, insulin resistance may be a common etiopathogenesis of RPL and RIF and insulin secretion impairment may be related to RIF.

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Idiopathic recurrent pregnancy loss - role of pre implantation genetic screening

10.26226/morressier.5912d9ead462b802923861f0 ◽

2017 ◽

Author(s):

Venkata Vellanki

Keyword(s):

Genetic Screening ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss

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Women with a History of Recurrent Pregnancy Loss Are a High-Risk Population for Adverse Obstetrical Outcome: A Retrospective Cohort Study

Journal of Clinical Medicine ◽

10.3390/jcm10020179 ◽

2021 ◽

Vol 10 (2) ◽

pp. 179

Author(s):

Emma Rasmark Roepke ◽

Ole Bjarne Christiansen ◽

Karin Källén ◽

Stefan R. Hansson

Keyword(s):

Cohort Study ◽

Preterm Birth ◽

Pregnancy Complications ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Placental Abruption ◽

Late Pregnancy ◽

High Risk Population ◽

Risk Population ◽

Increased Risk

Recurrent pregnancy loss (RPL), defined as three or more consecutive miscarriages, is hypothesized to share some of the same pathogenic factors as placenta-associated disorders. It has been hypothesized that a defect implantation causes pregnancy loss, while a partially impaired implantation may lead to late pregnancy complications. The aim of this retrospective register-based cohort study was to study the association between RPL and such disorders including pre-eclampsia, stillbirth, small for gestational age (SGA) birth, preterm birth and placental abruption. Women registered with childbirth(s) in the Swedish Medical Birth Register (MFR) were included in the cohort. Pregnancies of women diagnosed with RPL (exposed) in the National Patient Register (NPR), were compared with pregnancies of women without RPL (unexposed/reference). Obstetrical outcomes, in the first pregnancy subsequent to the diagnosis of RPL (n = 4971), were compared with outcomes in reference-pregnancies (n = 57,410). Associations between RPL and placental dysfunctional disorders were estimated by odds ratios (AORs) adjusting for confounders, with logistic regression. RPL women had an increased risk for pre-eclampsia (AOR 1.45; 95% CI; 1.24–1.69), stillbirth <37 gestational weeks (GWs) (AOR 1.92; 95% CI; 1.22–3.02), SGA birth (AOR 1.97; 95% CI; 1.42–2.74), preterm birth (AOR 1.46; 95% CI; 1.20–1.77), and placental abruption <37 GWs (AOR 2.47; 95% CI; 1.62–3.76) compared with pregnancies by women without RPL. Women with RPL had an increased risk of pregnancy complications associated with placental dysfunction. This risk population is, therefore, in need of improved antenatal surveillance.

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