Effect of extended oral contraception use on the prevalence of fetal trisomy 21 in women aged at least 35 years

Horányi, Dániel; Babay, Lilla Éva; Rigó, János; Győrffy, Balázs; Nagy, Gyula Richárd

doi:10.1002/ijgo.12238

Cited by 6 publications

(8 citation statements)

References 17 publications

(51 reference statements)

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“…61,62 Recent studies based on moderate doses of combined oral contraceptives in human showed a positive effect on trisomic pregnancies, miscarriages, and fecundity. 60,63,64,66,68,69 Therefore, some support for the ovulation hypothesis can be found among epidemiological data, but the overall lack of consensus rendered it important to test itin an experimentally tractable system. Some aspects of the maternal age effect cannot be explained by the ovulation hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Ovulation suppression protects against chromosomal abnormalities in mouse eggs at advanced maternal age

et al. 2021

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Section: Discussionmentioning

confidence: 99%

Ovulation suppression protects against chromosomal abnormalities in mouse eggs at advanced maternal age

et al. 2021

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“…If we accept that, according to this theory, the trisomic oocytes may be retarded in their maturation in comparison with normal oocytes, we have the possibility of reducing trisomic pregnancies with the preservation of the ovarian oocyte reserve by reducing the number of unnecessary ovulations. One method of oocyte reserve preservation is surprisingly obvious: the application of oral contraceptive pills reduces redundant ovulations …”

Section: Discussionmentioning

confidence: 99%

“…The number of disomic oocytes then drops faster than the small proportion of trisomic oocytes . The maternal age effect seems to be an accumulation of T21 oocytes in the ovarian reserve of older women due to the delay of these cells in maturation, which lag behind the normal cells . Hultén et al used fluorescence in situ hybridization (FISH) with two 21 chromosome‐specific probes to determine the copy number of chromosome 21 in ovarian cells from phenotypically normal fetuses at 14‐22 gestational weeks.…”

Section: Introductionmentioning

confidence: 99%

“…[5][6][7][8] The maternal age effect seems to be an accumulation of T21 oocytes in the ovarian reserve of older women due to the delay of these cells in maturation, which lag behind the normal cells. 9,10 Hultén et al 4 used fluorescence in situ hybridization (FISH) with two 21 chromosome-specific probes to determine the copy number of chromosome 21 in ovarian cells from phenotypically normal fetuses at 14-22 gestational weeks. They found that all the detected eight fetuses had T21 cells not only in meiotic but also in pre-meiotic mitotic and ovarian mesenchymal cells.…”

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Evidence for the Oocyte Mosaicism Selection model on the origin of Patau syndrome (trisomy 13)

Babay

Horányi

Győrffy

et al. 2019

Acta Obstet Gynecol Scand

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Introduction In 2008, Hultén et al hypothesized that maternal ovarian trisomy 21 mosaicism might be the primary causative factor for fetal Down syndrome. We hypothesize that this theory can be extended to trisomy 13. Material and methods We collected fetal ovarian tissue from seven female fetuses between 16 and 23 gestational weeks, following the termination of the pregnancy for non‐genetic reasons. All procedures were performed with informed consent and ethical approval from the local ethics committee. We used touch preparation techniques from fetal ovarian tissues and an anti‐stromal antigen 3 antibody against the meiosis‐specific stromal antigen 3 protein to differentiate between germ cells, ovarian stromal cells and the cells entering their first meiotic prophase. We used fluorescence in situ hybridization analysis to determine chromosome 13 numbers in each cell. Results We were able to detect a proportion of trisomy 13 cells in all cases. The average incidence of trisomy 13 cells was 2.04% in stromal antigen 3‐positive and 0.91% in the stromal antigen 3‐negative cells. The number of the trisomic cells increased significantly with gestational age (for stromal antigen 3‐positive cells r = 0.93, P = 0.0038, for stromal antigen 3‐negative cells r = 0.85, P = 0.0071). Conclusions This study indicates that besides trisomy 21, the Oocyte Mosaicism Selection model could be extended to trisomy 13 as well. The crucial factor for trisomy 13 seems to be the pre‐meiotic/mitotic trisomy 13 mosaicism, leading to a so‐called secondary meiotic nondisjunction of those oocytes having three copies of chromosome 13.

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“…Az ovulációgátló hatás következtében persze hosszú távon nem marad több petesejt a petefészekben, hiszen az apoptózis miatt a petesejtek száma folyamatosan csökken. Joggal feltételezhetjük azonban, hogy az apoptózis egyformán hat mind a triszómiás, mind a diszómiás petesejtekre, így az ovuláció gátlásakor a triszómiás/diszómiás petesejtek aránya nem változik [19,20]. Mivel az ovulációk fokozott számával a triszómiás/diszómiás petesejt arány romlik, az ovulációk gátlásával kedvezőbb arányszám "konzerválható".…”

Section: Az Orális Fogamzásgátlók Lehetséges Kedvező Hatása a Triszómiás Sejtek Arányáraunclassified

A terhességet megelőzően alkalmazott hosszabb távú orális fogamzásgátlás mint a magzati 21-es triszómia lehetséges kockázatcsökkentő tényezője idős anyai életkorban vállalt terhességben

et al. 2018

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Down syndrome is the most common autosomal chromosomal abnormality. According to the classical interpretation, it is the result of meiotic nondisjunction. Its occurrence is more common in advanced maternal age. Despite intensive research, pathophysiology of this genetic disorder is not fully understood. According to recent studies, a different kind of mechanism may be found in the background of trisomy 21 than was previously considered. Based on the ovarian mosaicism model, the cause of trisomy 21 (or any common trisomy) is a segregation error of a chromosome in premeiotic mitosis. The cell entering meiosis will be an oocyte with preexisting trisomy, where its (so-called "secondary") nondisjunction is essential. Maturation of the trisomic oocytes appears to fall behind the disomic oocytes, resulting in their relative accumulation in the ovaries as time progresses. The ratio of trisomic/disomic cells becomes less favorable in maternal maturity. If ovulation is inhibited - although the number of oocytes will continue to decline due to apoptosis - it can be assumed that the trisomic/disomic oocyte ratio remains more favorable with the progression of age. In our summary report, presenting and updating our previous data, we would like to propose that - according to ovarian mosaicism model - long-term oral contraception in the anamnesis may be beneficial in pregnancies with advanced maternal age. Orv Hetil. 2018; 159(28): 1146-1152.

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Effect of extended oral contraception use on the prevalence of fetal trisomy 21 in women aged at least 35 years

Abstract: Fewer ovulatory cycles, potentially resulting from longer oral contraceptive pill use, was associated with healthy fetal karyotypes among patients of advanced reproductive age.

Cited by 6 publications

References 17 publications

Ovulation suppression protects against chromosomal abnormalities in mouse eggs at advanced maternal age

Ovulation suppression protects against chromosomal abnormalities in mouse eggs at advanced maternal age

Evidence for the Oocyte Mosaicism Selection model on the origin of Patau syndrome (trisomy 13)

A terhességet megelőzően alkalmazott hosszabb távú orális fogamzásgátlás mint a magzati 21-es triszómia lehetséges kockázatcsökkentő tényezője idős anyai életkorban vállalt terhességben

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