PGD for fragile X syndrome: ovarian function is the main determinant of success.
BACKGROUND
PGD for fragile X syndrome (FRAX) is inefficient, probably owing to fewer oocytes, poor embryo quality and difficulties in genetic analysis. We investigated IVF-PGD in FRAX mutation carriers compared with controls, looking at the effects of oocyte and embryo number/quality on live birth outcome.


METHODS
We performed IVF-PGD in 27 patients with the FRAX mutation and 33 controls with other genetic diseases. Genetic testing was by multiplex PCR.


RESULTS
Seventy-nine and 108 IVF-PGD cycles were started in FRAX mutation carriers and controls, respectively. Twenty-two patients had a premutation (CGG repeat number 60-200) and five had a full mutation (300-2000 CGG repeats). FRAX patients required higher doses of gonadotrophins (6788 ± 2379 versus 4360 ± 2330, P< 0.001) but had lower peak serum estradiol levels (8166 ± 5880 versus 10 211 ± 4673, P = 0.03) and fewer oocytes retrieved (9.8 ± 6 versus 14 ± 8, P = 0.01). The cancellation rate (unsatisfactory ovarian response) was higher in the FRAX group than in the control group (13 versus 1%, P < 0.001). When embryos were transferred, ongoing pregnancy/live birth rates per transfer were similar (29 versus 36%, P = 0.54).


CONCLUSIONS
Ovarian dysfunction in FRAX carriers is more prevalent and profound than previously appreciated, with a high cancelation rate and reduced efficiency of PGD. The main determinant for successful PGD for FRAX is ovarian dysfunction. When embryo transfer is possible, the results are comparable to PGD for other monogenic diseases.
Tsafrir
Avi
A
IVF Unit, Department of Obstetrics and Gynecology, Shaare-Zedek Medical Center, Hebrew University Medical School, Jerusalem, Israel. avits@szmc.org.il
Altarescu
Gheona
G
Margalioth
Ehud
E
Brooks
Baruch
B
Renbaum
Paul
P
Levy-Lahad
Ephrat
E
Rabinowitz
Ron
R
Varshaver
Irit
I
Eldar-Geva
Talia
T
D000328:Adult; D006063:Chorionic Gonadotropin / Q000627:therapeutic use; D015331:Cohort Studies; D004958:Estradiol / Q000097:blood; D005260:Female; D005300:Fertility Agents, Female / Q000627:therapeutic use; D005307:Fertilization in Vitro / Q000379:methods; D005600:Fragile X Syndrome / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D050498:Live Birth / Q000235:genetics; D008297:Male; D009154:Mutation; D054315:Oocyte Retrieval; D010053:Ovary; D010062:Ovulation Induction / Q000379:methods; D011247:Pregnancy; D018873:Pregnancy Rate; D019836:Preimplantation Diagnosis / Q000379:methods*; D012680:Sensitivity and Specificity
D006063:Chorionic Gonadotropin; D005300:Fertility Agents, Female; D004958:Estradiol