Table 3.
ICSI/PGT cycle and ovarian response in BRCA mutation carriers and controls
| ICSI/PGT cycle | BRCA mutation carrier (n = 31) | Sig.* | BRCA1 mutation carrier (n = 17) | Sig.* | BRCA2 mutation carrier (n = 14) | Sig.* | Control (n = 107) |
|---|---|---|---|---|---|---|---|
| Received treatment | |||||||
| Long-agonist with oral contraceptive | 24 (77.4%) | 0.03 | 14 (82.4%) | 0.21 | 10 (71.4%) | 0.04 | 98 (91.6%) |
| Stimulating medicine | 0.01 | 0.27 | 0.01 | ||||
| rFSH | 21 (67.7%) | 13 (76.5%) | 8 (57.1%) | 93 (86.9%) | |||
| uFSH | 10 (32.3%) | 4 (23.5%) | 6 (42.9%) | 14 (13.1%) | |||
| Start dose FSH | |||||||
| 150/day | 22 (71.0%) | 0.56 | 12 (70.6%) | 0.68 | 10 (71.4%) | 0.77 | 70 (65.4%) |
| 187.5/day | 1 (3.2%) | 0.40 | 0 (0%) | 1.000 | 1 (7.1%) | 0.22 | 1 (0.9%) |
| 200/day | 0 (0%) | 1.000 | 0 (0%) | 1.000 | 0 (0%) | 1.000 | 1 (0.9%) |
| 225/day | 8 (25.8%) | 0.47 | 5 (29.4%) | 0.79 | 3 (21.4%) | 0.55 | 35 (32.7%) |
| Dose adjustments (FSH) | |||||||
| Dose increased | 6 (19.4%) | 0.02 | 4 (23.5%) | 0.02 | 2 (14.3%) | 0.19 | 5 (4.7%) |
| Dose decreased | 0 (0%) | NA | 0 (0%) | NA | 0 (0%) | NA | 0 (0%) |
| Received cumulative dose FSH | 1925 (± 543) | 0.78 | 2122 (± 778) | 0.59 | 1769 (± 270) | 0.43 | 1959 (± 567) |
| Number of days stimulated | 11.3 (± 2.0) | 0.78 | 11.5 (± 2.8) | 0.70 | 11.1 (± 1.9) | 0.82 | 11.1 (± 2.0) |
| Hyper response | 5 (16.1%) | 0.66 | 1 (5.9%) | 0.30 | 4 (28.6%) | 0.48 | 21 (19.6%) |
| - Cancelled follicular punction | 1 (3.2%) | 0 (0%) | 1 (7.1%) | 4 (3.7%) | |||
| - > 15 oocytes at follicle aspiration | 4 (12.9%) | 1 (5.9%) | 3 (21.4%) | 17 (15.9%) | |||
| Low response | |||||||
| Low response | 7 (22.6%) | 0.06 | 4 (23.5%) | 0.10 | 3 (21.4%) | 0.17 | 10 (9.3%) |
| Unexpected low responsea | 5 (71.4%) | 3 (75.0%) | 2 (66.7%) | 3 (30.0%) | |||
| - Cancelled oocyte retrieval | 5 (16.1%) | 3 (75.0%) | 2 (66.7%) | 6 (5.6%) | |||
| - < 4 oocytes at retrieval | 2 (6.5%) | 1 (25.0%) | 1 (33.3%) | 4 (3.7%) | |||
| Odds-ratio (95% CI) for low response | |||||||
| Unadjusted | 2.83 (0.98–8.20) | 0.06 | 2.99 (0.82–10.91) | 0.10 | 2.65 (0.63–11.09) | 0.18 | |
| Age-adjusted | 3.16 (1.04–9.67) | 0.04 | 2.91 (0.77–11.00) | 0.12 | 3.56 (0.79–16.07) | 0.10 | |
| Fully-adjustedb | 3.47 (0.85–14.21) | 0.08 | 2.91 (0.50–16.93) | 0.23 | 3.98 (0.66–24.18) | 0.13 | |
| Oocyte retrieval performed | BRCA mutation carrier (n = 25) | Sig.* | BRCA1 mutation carrier (n = 14) | Sig.* | BRCA2 mutation carrier (n = 11) | Sig.* | Control (n = 96) |
| 80.6% | 82.4% | 78.6% | 89.7% | ||||
| Total oocytes | 9 (6–14) | 0.36 | 9 (6–12) | 0.32 | 9 (4–16) | 0.75 | 10 (7–13) |
| Mature (MII) oocytes | 7 (5–10) | 0.23 | 7 (5–10) | 0.33 | 7 (4–10) | 0.41 | 8 (6–12) |
| Fraction biopsiedc | 0.59 (± 0.24) | 0.51 | 0.56 (± 0.20) | 0.29 | 0.63 (± 0.29) | 0.92 | 0.63 (± 0.23) |
| Mancova, Wilk’s Lambda sig.d | |||||||
| Unadjusted | 0.72 | 0.55 | 0.90 | ||||
| Age-adjusted | 0.74 | 0.63 | 0.87 | ||||
| Fully-adjustedb | 0.84 | 0.76 | 0.68 | ||||
| Pregnancy per started cycle | BRCA mutation carrier (n = 31) | Sig.* | BRCA1 mutation carrier (n = 17) | Sig.* | BRCA2 mutation carrier (n = 14) | Sig.* | Control (n = 107) |
| Cycles with embryo transfer (SET) | 22 (71.0%) | 0.75 | 12 (70.6%) | 0.77 | 10 (71.4%) | 1.000 | 79 (73.8%) |
| Pregnancy | 8 (25.6%) | 0.78 | 4 (23.5%) | 1.000 | 2 (14.3%) | 1.000 | 25 (23.4%) |
| Biochemical pregnancy, miscarriage or molar pregnancy | 4 (12.9%) | 2 (11.8%) | 0 (0%) | 7 (6.5%) | |||
| Ongoing clinical pregnancye | 4 (12.9%) | 2 (11.8%) | 2 (14.3%) | 18 (16.8%) | |||
| Odds-ratio (95% CI) for ongoing pregnancy | |||||||
| Unadjusted | 0.81 (0.28–2.32) | 0.69 | 0.71 (0.15–3.37) | 0.66 | 0.88 (0.18–4.30) | 0.88 | |
| Age-adjusted | 0.81 (0.28–2.33) | 0.70 | 0.66 (0.14–3.18) | 0.61 | 0.96 (0.20–4.76) | 0.96 | |
| Fully-adjustedb | 1.05 (0.30–3.64) | 0.94 | 1.02 (0.17–6.18) | 0.98 | 1.43 (0.23–8.83) | 0.70 | |
rFSH/uFSH, recombinant/urinary follicle-stimulating hormone; CI, confidence interval; SET, single embryo transfer; NA, not applicable. Values presented as number (%) in categorical variables, values presented as mean (SD) or median (IQR) in continuous variables. *P-values comparing values in carriers vs controls, calculated using Fisher’s exact/chi-square or Mann–Whitney U/T-test. aLow response was expected in females with AMH < 0.96 ng/ml or AFC 0–7. bAdjusted for age, BMI, gravidity, smoking, oral contraceptive use in downregulation, type- and cumulative dosage of administered gonadotropin. cNumber of embryos that was biopsied, divided by the number of retrieved oocytes. dLevel of significance for variance in total oocytes, mature oocytes or fraction biopsied, explained by BRCA carrier status. eOngoing clinical pregnancy with foetal heartbeat at 7 weeks of gestation