Maureen Franssen

Reproductive outcome after PGD in couples with recurrent miscarriage carrying a structural chromosome abnormality: a systematic review

BACKGROUNDnPreimplantation genetic diagnosis (PGD) has been stated to improve live birth rates compared with natural conception in couples with recurrent miscarriage (RM) carrying a structural chromosome abnormality. It is unclear to what extent this claim can be substantiated by evidence. A systematic review of the literature was performed on the reproductive outcome of these couples after natural conception or after PGD.nnnMETHODSnMEDLINE, EMBASE and the Cochrane database were searched until April 2009. Trials, patient series and case reports describing reproductive outcome in couples with RM carrying a structural chromosome abnormality after natural conception and/or after PGD were included. Since no randomized controlled trials or non-randomized comparative studies were found, separate searches for both groups were conducted. Primary outcome measure was live birth rate per couple. Secondary outcome measure was miscarriage rate per couple.nnnRESULTSnFour observational studies reporting on the reproductive outcome of 469 couples after natural conception and 21 studies reporting on the reproductive outcome of 126 couples after PGD were found. After natural conception, live birth rate per couple varied between 33 and 60% (median 55.5%) after parental chromosome analysis; miscarriage rate ranged from 21 to 40% (median 34%). After PGD, live birth rate per couple varied between 0 and 100% (median 31%) after parental chromosome analysis; miscarriage rate ranged from 0 to 50% (median 0%).nnnCONCLUSIONSnCurrently, there are insufficient data indicating that PGD improves the live birth rate in couples with RM carrying a structural chromosome abnormality.

Consecutive or non-consecutive recurrent miscarriage: is there any difference in carrier status?

BACKGROUNDnCarrier status of a structural balanced chromosome abnormality is associated with recurrent miscarriage. There is, at present, no evidence of the impact of the sequence of preceding pregnancies on the probability of carrier status. The aim of our study was therefore to examine whether the history of consecutive versus non-consecutive miscarriages in couples with two or more miscarriages has any impact on the probability of carrying a chromosome abnormality.nnnMETHODSnA nested case-control study was performed in six centres for clinical genetics in the Netherlands. Couples referred for chromosome analysis after two or more miscarriages were included: 279 couples with a carrier of a structural chromosomal abnormality and 428 non-carrier couples who served as controls. Univariable and multivariable logistic regression analyses, corrected for known risk factors for carrier status, were performed. The main outcome measure was the probability of carrier status.nnnRESULTSnTwo hundred and fifty-six of 279 (92%) carrier couples and 381 of 428 (89%) non-carrier couples had experienced consecutive miscarriages (P = 0.21). A history of two or three consecutive miscarriages did not alter the probability of carrier status when compared with two [odds ratio (OR) 0.90, 95% confidence interval (CI) 0.48-1.7] or three (OR 0.71, 95% CI 0.39-1.3) non-consecutive miscarriages.nnnCONCLUSIONSnThe sequence of preceding pregnancies is not a risk factor for carrier status. Therefore, couples with miscarriages interspersed with healthy child(ren) should be managed the same as couples with consecutive miscarriages regarding chromosome diagnosis.

Inherited unbalanced structural chromosome abnormalities at prenatal chromosome analysis are rarely ascertained through recurrent miscarriage

To determine the mode of ascertainment of inherited unbalanced structural chromosome abnormalities detected at prenatal chromosome analysis.

Low uptake of prenatal diagnosis after established carrier status of a balanced structural chromosome abnormality in couples with recurrent miscarriage

OBJECTIVEnTo evaluate to what extent couples carrying a balanced structural chromosome abnormality follow up the advice to opt for invasive prenatal diagnosis (PND) in subsequent pregnancies.nnnDESIGNnIndex-control study.nnnSETTINGnSix centers for Clinical Genetics in The Netherlands.nnnPATIENT(S)nCouples referred for chromosome analysis after recurrent miscarriage between 1992 and 2001 and with at least one pregnancy after disclosure; 239 carrier couples and 389 noncarrier couples.nnnINTERVENTION(S)nQuestionnaire, medical record checking.nnnMAIN OUTCOME MEASURE(S)nUptake of invasive PND.nnnRESULT(S)nOnly 53 of 239 (22%) carrier couples underwent a PND procedure (CVS or amniocentesis) in all subsequent pregnancies. A relatively high number, 105 (44%) carrier couples, refrained from PND in all subsequent pregnancies. More carrier couples with maternal age >or=36 years (20/33 = 61%) refrained from PND, compared with carrier couples with maternal age <36 years (85/206 = 41%). In women >or=36 years, an equal proportion of carrier and noncarrier couples refrained from PND (61% vs. 54%).nnnCONCLUSION(S)nThe advice to opt for invasive PND in carrier couples is poorly followed, especially in carrier couples with maternal age >or=36 years. The motivations of carrier couples to opt for or refrain from invasive PND procedures should be the topic for further research to optimize clinical care and informative decision making.