Editing Recurrent miscarriage (section)

=== Parental and genetic factors ===

* '''Advanced maternal age:''' [[Advanced maternal age|Maternal age]] is associated with increased risk of miscarriage with a rate of 50% in women over 40 years of age. This higher likelihood of pregnancy loss can be attributed to the higher incidence of trisomies, a chromosomal abnormality, seen in women over the age of 35.<ref name="Fertility and Sterility_2012_2" />
* '''Chromosomal abnormalities:''' Recurrent pregnancy loss is most commonly found to be caused by [[Chromosome abnormality|chromosomal abnormalities]] in the fetus, accounting for approximately 50% of cases. These include structural aberrations (such as chromosomal inversions, insertions, deletions, and translocations) and numerical aberrations, also called [[Aneuploidy|aneuploidies]] (trisomies, monosomy X, and triploidy).<ref name="Lei_2022" /> These can be detected by cytogenetic testing such as [[Karyotype|karyotyping]] (test that analyzes the structure and quantity of chromosomes), [[Fluorescence in situ hybridization|FISH]], MLPA, aCGH, and SNP array.<ref name="Smits_2020">{{cite journal | vauthors = Smits MA, van Maarle M, Hamer G, Mastenbroek S, Goddijn M, van Wely M | title = Cytogenetic testing of pregnancy loss tissue: a meta-analysis | journal = Reproductive Biomedicine Online | volume = 40 | issue = 6 | pages = 867–879 | date = June 2020 | pmid = 32417200 | doi = 10.1016/j.rbmo.2020.02.001 | doi-access = free }}</ref> Some research suggests that chromosomal abnormalities occur more frequently in sporadic pregnancy loss than in recurrent pregnancy loss, and the incidence of RPL is lower in women with 3 or more pregnancy losses.<ref name="Lei_2022" /> Parental chromosomal abnormalities is a rare cause of RPL, found in approximately 2-4% cases. Studies comparing pregnancy outcomes in couples experiencing RPL with and without chromosomal abnormalities found that parental carriers of chromosomal abnormalities had a lower live birth rate, specifically carriers of a reciprocal/balanced [[Robertsonian translocation]]. This evidence suggests that although RPL can occur in both couples with and without chromosomal aberrations, those that do are at higher risk of pregnancy loss.<ref>{{cite journal | vauthors = Li S, Zheng PS, Ma HM, Feng Q, Zhang YR, Li QS, He JJ, Liu WF | display-authors = 6 | title = Systematic review of subsequent pregnancy outcomes in couples with parental abnormal chromosomal karyotypes and recurrent pregnancy loss | journal = Fertility and Sterility | volume = 118 | issue = 5 | pages = 906–914 | date = November 2022 | pmid = 36175209 | doi = 10.1016/j.fertnstert.2022.08.008 | doi-access = free }}</ref> Previous studies produced conflicting results. Genetic evaluation of RPL is generally recommended in order to determine the need for genetic counseling and appropriate treatment.<ref name="Fertility and Sterility_2012_2" /> This, however, can differ among medical societies where others recommend against routine cytogenetic testing for couples experiencing RPL as it is of little clinical benefit.<ref name="Bender Atik_2018">{{cite journal | vauthors = Bender Atik R, Christiansen OB, Elson J, Kolte AM, Lewis S, Middeldorp S, Nelen W, Peramo B, Quenby S, Vermeulen N, Goddijn M | display-authors = 6 | title = ESHRE guideline: recurrent pregnancy loss | journal = Human Reproduction Open | volume = 2018 | issue = 2 | pages = hoy004 | date = 2018-04-01 | pmid = 31486805 | pmc = 6276652 | doi = 10.1093/hropen/hoy004 }}</ref> It is instead considered after individual risk assessment (ie. family history) and recommended to test parental chromosomes rather than the [[products of conception]].<ref name="Smits_2020" /><ref name="Bender Atik_2018" />
* '''Paternal Factors:''' There is emerging research that suggests male factors may contribute to recurrent pregnancy loss. A systematic review found that sperm DNA fragmentation, defined as breaks in the DNA strand of sperm cells, may be associated with RPL. Their findings included higher rates of SDF and other sperm parameters (ie. lower sperm number, motility, or ejaculation volume) in men experiencing RPL. No evidence of a relationship between RPL and paternal age, BMI, smoking, or alcohol use.<ref>{{Cite journal |last1=Inversetti |first1=Annalisa |last2=Bossi |first2=Arianna |last3=Cristodoro |first3=Martina |last4=Larcher |first4=Alessandro |last5=Busnelli |first5=Andrea |last6=Grande |first6=Giuseppe |last7=Salonia |first7=Andrea |last8=Simone |first8=Nicoletta Di |date=2023-10-25 |title=Recurrent pregnancy loss: a male crucial factor—A systematic review and meta-analysis |journal=Andrology |language=en |doi=10.1111/andr.13540 |pmid=37881014 |issn=2047-2919|doi-access=free }}</ref> The European Association of Urology Guidelines on Sexual and Reproductive Health therefore recommends SDF testing in cases of infertility or recurrent pregnancy loss.<ref>{{Cite journal |last1=Minhas |first1=Suks |last2=Bettocchi |first2=Carlo |last3=Boeri |first3=Luca |last4=Capogrosso |first4=Paolo |last5=Carvalho |first5=Joana |last6=Cilesiz |first6=Nusret Can |last7=Cocci |first7=Andrea |last8=Corona |first8=Giovanni |last9=Dimitropoulos |first9=Konstantinos |last10=Gül |first10=Murat |last11=Hatzichristodoulou |first11=Georgios |last12=Jones |first12=Thomas Hugh |last13=Kadioglu |first13=Ates |last14=Martínez Salamanca |first14=Juan Ignatio |last15=Milenkovic |first15=Uros |date=November 2021 |title=European Association of Urology Guidelines on Male Sexual and Reproductive Health: 2021 Update on Male Infertility |url=https://linkinghub.elsevier.com/retrieve/pii/S0302283821019825 |journal=European Urology |language=en |volume=80 |issue=5 |pages=603–620 |doi=10.1016/j.eururo.2021.08.014|pmid=34511305 |s2cid=237492693 |hdl=10216/136115 |hdl-access=free }}</ref>