Merck - Feasibility analysis

Efficacy in women undergoing IVF/ICSI with stimulation with Pergoveris to that of hMG in terms of clinical outcomes

Author
Affiliation

Andrea Francavilla, MD, Biostatistician

FROM - Fondazione per la ricerca Ospedale di Bergamo - ETS

Published

07-06-2024

1 OPERA - data availability

In OPERA database, a total of 106.551 cycles can be identified. After the following procedure:

  • Removal of duplicates (1573 cycles)

  • Removal of thawing cycles without any previous stimulation cycle (2402 thawing cycles)

  • Removal of thawing cycles with an additional thawing cycle as their originating cycle (1700 thawing cycles)

102.157 cycles can be identified (Please note that a cycle could be a duplicate and a thawing cycle with no parent cycle at the same time, so the grand number cannot be derived by a simple subtraction).

These 102.157 cycles can be separated as follows:

  • 69.993 stimulated cycles

  • 32.164 thawing cycles

2 Data suitable for MERCK - feasibility analysis

Out of all OPERA cycles , the number of cycles stimulated with only Pergoveris or only hMg is 41.783. In fact, around 2.000 cycles are further not considered in the following feasibility analysis due to the usage of multiple stimulation drugs at the same time.

These 41.783 cycles can be separated as follows:

  • 29.786 stimulated cycles, of whom: 15.081 stimulated with Pergoveris and 14.705 with hMG

  • 11.097 thawing cycles derived from the 29.786 stimulation cycles above mentioned.

When Pergoveris was used for stimulation, a total of 22.314 cycles can be identified (15.081 stimulation cycles + 7.233 thawing cycles).

When hMg was used for stimulation, a total of 19.469 cycles can be identified (14.705 stimulation cycles + 4.764 thawing cycles).

2.0.1 Statistical considerations

In order to better answer to your clinical questions, the unit of analysis consists of an originating stimulation cycle ± any thawing cycle derived from the previous one. It means that we considered a series of cycles from the woman(e.g., stimulation + thawing + thawing) as the same patient undergoing multiple procedures, but if multiple stimulation cycles come with multiple thawing cycles for each stimulation cycle, they are kept as separated (e.g., stimulation + thawing + stimulation + thawing): we considered these as two different patients( stimulation + thawing | stimulation + thawing) even if in fact they belong to the same person.

3 Baseline characteristics

Baseline characteristics are presented for stimulation cycles only (any thawing cycle is excluded).

Baseline characteristics
First stimulation cycle in OPERA database
Overall, N = 29.7861 Gn used for stimulation
hMg, N = 14.7051 Pergoveris, N = 15.0811
Age of woman


    N (% not missing) 29.786 (100%) 14.705 (100%) 15.081 (100%)
    Median (25%-75%) 38 (34-40) 38 (35-41) 37 (33-39)
    Range 19, 52 19, 50 20, 52
    Mean (SD) 37 (4) 38 (4) 36 (4)
    N missing (% missing) 0 (0%) 0 (0%) 0 (0%)
BMI


    N (% not missing) 29.080 (98%) 14.181 (96%) 14.899 (99%)
    Median (25%-75%) 23 (21-26) 22 (20-25) 23 (21-26)
    Range 15, 45 15, 45 15, 45
    Mean (SD) 24 (5) 23 (4) 24 (5)
    N missing (% missing) 706 (2%) 524 (4%) 182 (1%)
Age of man


    N (% not missing) 29.725 (100%) 14.672 (100%) 15.053 (100%)
    Median (25%-75%) 40 (36-44) 40 (37-44) 39 (36-43)
    Range 20, 78 20, 76 20, 78
    Mean (SD) 40 (6) 41 (6) 40 (6)
    N missing (% missing) 61 (0%) 33 (0%) 28 (0%)
Duration of sterility


    N (% not missing) 23.199 (78%) 10.284 (70%) 12.915 (86%)
    Median (25%-75%) 4 (3-6) 4 (3-6) 4 (2-6)
    Range 0, 25 0, 25 0, 24
    Mean (SD) 5 (3) 5 (3) 4 (3)
    N missing (% missing) 6.587 (22%) 4.421 (30%) 2.166 (14%)
Female infertility 18.347 / 28.250 (65%) 9.235 / 13.571 (68%) 9.112 / 14.679 (62%)
    N missing (% missing) 1.536 / 29.786 (5%) 1.134 / 14.705 (8%) 402 / 15.081 (3%)
Cause of female infertility


    Other 11.343 / 18.347 (62%) 6.029 / 9.235 (65%) 5.314 / 9.112 (58%)
    Endometrial factor 3.235 / 18.347 (18%) 1.429 / 9.235 (15%) 1.806 / 9.112 (20%)
    Tubal factor 3.036 / 18.347 (17%) 1.540 / 9.235 (17%) 1.496 / 9.112 (16%)
    Uterine factor 733 / 18.347 (4%) 237 / 9.235 (3%) 496 / 9.112 (5%)
    N missing (% missing) 11.439 / 29.786 (38%) 5.470 / 14.705 (37%) 5.969 / 15.081 (40%)
AMH


    N (% not missing) 17.492 (59%) 9.049 (62%) 8.443 (56%)
    Median (25%-75%) 2 (1-3) 2 (1-3) 2 (1-3)
    Range 0, 113 0, 113 0, 98
    Mean (SD) 3 (4) 2 (4) 3 (5)
    N missing (% missing) 12.294 (41%) 5.656 (38%) 6.638 (44%)
AFC


    N (% not missing) 501 (2%) 495 (3%) 6 (0%)
    Median (25%-75%) 8 (5-12) 8 (5-12) 11 (10-12)
    Range 0, 26 0, 26 0, 14
    Mean (SD) 9 (5) 9 (5) 10 (5)
    N missing (% missing) 29.285 (98%) 14.210 (97%) 15.075 (100%)
Sperm source


    Fresh 27.697 / 29.786 (93%) 13.854 / 14.705 (94%) 13.843 / 15.081 (92%)
    Frozen 2.089 / 29.786 (7%) 851 / 14.705 (6%) 1.238 / 15.081 (8%)
    N missing (% missing) 0 / 29.786 (0%) 0 / 14.705 (0%) 0 / 15.081 (0%)
N° of previous cycles


    N (% not missing) 29.786 (100%) 14.705 (100%) 15.081 (100%)
    Median (25%-75%) 1 (0-3) 1 (0-3) 1 (0-3)
    Range 0, 30 0, 24 0, 30
    Mean (SD) 2 (3) 2 (3) 2 (3)
    N missing (% missing) 0 (0%) 0 (0%) 0 (0%)
GnRH analog


    GnRH antagonist 22.310 / 29.786 (75%) 10.689 / 14.705 (73%) 11.621 / 15.081 (77%)
    GnRH agonist 6.161 / 29.786 (21%) 3.197 / 14.705 (22%) 2.964 / 15.081 (20%)
    No 1.315 / 29.786 (4%) 819 / 14.705 (6%) 496 / 15.081 (3%)
    N missing (% missing) 0 / 29.786 (0%) 0 / 14.705 (0%) 0 / 15.081 (0%)
Oocyte triggering


    rhCG trigger 14.791 / 27.433 (54%) 7.941 / 13.122 (61%) 6.850 / 14.311 (48%)
    GnRHa alone or in combination 5.821 / 27.433 (21%) 991 / 13.122 (8%) 4.830 / 14.311 (34%)
    uhCG trigger 4.019 / 27.433 (15%) 2.523 / 13.122 (19%) 1.496 / 14.311 (10%)
    Other 2.802 / 27.433 (10%) 1.667 / 13.122 (13%) 1.135 / 14.311 (8%)
    N missing (% missing) 2.353 / 29.786 (8%) 1.583 / 14.705 (11%) 770 / 15.081 (5%)
LPS support 18.736 / 29.786 (63%) 8.706 / 14.705 (59%) 10.030 / 15.081 (67%)
    N missing (% missing) 0 / 29.786 (0%) 0 / 14.705 (0%) 0 / 15.081 (0%)
Modality of LPS suppport


    Vaginal 9.356 / 18.734 (50%) 5.187 / 8.705 (60%) 4.169 / 10.029 (42%)
    Oral 4.083 / 18.734 (22%) 2.078 / 8.705 (24%) 2.005 / 10.029 (20%)
    Mixed 2.913 / 18.734 (16%) 1.267 / 8.705 (15%) 1.646 / 10.029 (16%)
    Injection 2.153 / 18.734 (11%) 168 / 8.705 (2%) 1.985 / 10.029 (20%)
    Nasal 229 / 18.734 (1%) 5 / 8.705 (0%) 224 / 10.029 (2%)
    N missing (% missing) 11.052 / 29.786 (37%) 6.000 / 14.705 (41%) 5.052 / 15.081 (33%)
Gn, total dose


    N (% not missing) 26.804 (90%) 14.614 (99%) 12.190 (81%)
    Median (25%-75%) 2.275 (1.650-3.000) 2.250 (1.600-3.000) 2.325 (1.650-2.850)
    Range 100, 7.500 100, 7.350 150, 7.500
    Mean (SD) 2.367 (1.011) 2.399 (1.100) 2.329 (890)
    N missing (% missing) 2.982 (10%) 91 (1%) 2.891 (19%)
Days of stimulation


    N (% not missing) 29.784 (100%) 14.704 (100%) 15.080 (100%)
    Median (25%-75%) 10 (8-11) 9 (8-11) 10 (9-11)
    Range 1, 75 1, 54 1, 75
    Mean (SD) 10 (3) 10 (3) 10 (2)
    N missing (% missing) 2 (0%) 1 (0%) 1 (0%)
Gn, dose per day


    N (% not missing) 26.785 (90%) 14.614 (99%) 12.171 (81%)
    Median (25%-75%) 250 (182-300) 250 (188-300) 245 (175-300)
    Range 8, 750 13, 600 8, 750
    Mean (SD) 244 (82) 249 (89) 238 (73)
    N missing (% missing) 3.001 (10%) 91 (1%) 2.910 (19%)
1 n / N (%)

4 Outcomes: Fresh cycles

The following outcomes are reported for all the stimulation cycles, even if embryo-transfer was not performed. Due to this reason, the same outcomes are reported once again for the % of cycles going to embryo-transfer. LPS support, already presented in the previous table, is presented again for stimulation cycles that reached embryo-transfer.

Outcomes: All stimulated cycles, regardless of embryo-transfer
Overall, N = 29.7861 Gn used for stimulation
hMg, N = 14.7051 Pergoveris, N = 15.0811
Cycles without fresh embryo-transfer 8.631 / 29.786 (29%) 4.840 / 14.705 (33%) 3.791 / 15.081 (25%)
Method of fertilization


    ICSI 19.610 / 27.149 (72%) 9.330 / 12.781 (73%) 10.280 / 14.368 (72%)
    IVF 6.677 / 27.149 (25%) 3.194 / 12.781 (25%) 3.483 / 14.368 (24%)
    Both 862 / 27.149 (3.2%) 257 / 12.781 (2.0%) 605 / 14.368 (4.2%)
    N missing (% missing) 2.637 / 29.786 (8.9%) 1.924 / 14.705 (13%) 713 / 15.081 (4.7%)
N° oocytes retrieved


    N (% not missing) 29.765 (100%) 14.685 (100%) 15.080 (100%)
    Median (25%-75%) 6 (3-11) 5 (2-9) 8 (4-13)
    Range 0, 76 0, 51 0, 76
    Mean (SD) 8 (6) 6 (5) 9 (7)
    N missing (% missing) 21 (<0.1%) 20 (0.1%) 1 (<0.1%)
N° of M2 oocytes


    N (% not missing) 29.765 (100%) 14.685 (100%) 15.080 (100%)
    Median (25%-75%) 3.0 (0.0-7.0) 3.0 (0.0-6.0) 3.0 (0.0-8.0)
    Range 0.0, 39.0 0.0, 33.0 0.0, 39.0
    Mean (SD) 4.2 (4.8) 3.8 (4.2) 4.7 (5.4)
    N missing (% missing) 21 (<0.1%) 20 (0.1%) 1 (<0.1%)
N° of 2PN


    N (% not missing) 29.786 (100%) 14.705 (100%) 15.081 (100%)
    Median (25%-75%) 3.0 (1.0-6.0) 2.0 (1.0-5.0) 4.0 (2.0-7.0)
    Range 0.0, 44.0 0.0, 29.0 0.0, 44.0
    Mean (SD) 4.0 (3.8) 3.1 (3.0) 4.9 (4.2)
    N missing (% missing) 0 (0%) 0 (0%) 0 (0%)
N° embryos cryopreserved


    0 22.366 / 29.786 (75%) 11.298 / 14.705 (77%) 11.068 / 15.081 (73%)
    1 3.097 / 29.786 (10%) 1.486 / 14.705 (10%) 1.611 / 15.081 (11%)
    2 2.189 / 29.786 (7.3%) 936 / 14.705 (6.4%) 1.253 / 15.081 (8.3%)
    ≥3 2.134 / 29.786 (7.2%) 985 / 14.705 (6.7%) 1.149 / 15.081 (7.6%)
    N missing (% missing) 0 / 29.786 (0%) 0 / 14.705 (0%) 0 / 15.081 (0%)
N° oocytes cryopreserved


    0 29.428 / 29.786 (99%) 14.378 / 14.705 (98%) 15.050 / 15.081 (100%)
    ≥1 358 / 29.786 (1.2%) 327 / 14.705 (2.2%) 31 / 15.081 (0.2%)
    N missing (% missing) 0 / 29.786 (0%) 0 / 14.705 (0%) 0 / 15.081 (0%)
N° of transfered embryos


    1 9.876 / 28.755 (34%) 4.938 / 14.602 (34%) 4.938 / 14.153 (35%)
    2 9.671 / 28.755 (34%) 4.498 / 14.602 (31%) 5.173 / 14.153 (37%)
    0 8.625 / 28.755 (30%) 4.837 / 14.602 (33%) 3.788 / 14.153 (27%)
    3 582 / 28.755 (2.0%) 328 / 14.602 (2.2%) 254 / 14.153 (1.8%)
    4 1 / 28.755 (<0.1%) 1 / 14.602 (<0.1%) 0 / 14.153 (0%)
    N missing (% missing) 1.031 / 29.786 (3.5%) 103 / 14.705 (0.7%) 928 / 15.081 (6.2%)
Stage of embryo development at transfer


    D5 8.004 / 20.123 (40%) 2.552 / 9.759 (26%) 5.452 / 10.364 (53%)
    D3 7.678 / 20.123 (38%) 4.565 / 9.759 (47%) 3.113 / 10.364 (30%)
    D2 3.707 / 20.123 (18%) 2.437 / 9.759 (25%) 1.270 / 10.364 (12%)
    D4 637 / 20.123 (3.2%) 148 / 9.759 (1.5%) 489 / 10.364 (4.7%)
    D6 97 / 20.123 (0.5%) 57 / 9.759 (0.6%) 40 / 10.364 (0.4%)
    N missing (% missing) 9.663 / 29.786 (32%) 4.946 / 14.705 (34%) 4.717 / 15.081 (31%)
N° of gestional sacs


    0 22.327 / 28.572 (78%) 11.856 / 14.434 (82%) 10.471 / 14.138 (74%)
    1 5.304 / 28.572 (19%) 2.197 / 14.434 (15%) 3.107 / 14.138 (22%)
    2 924 / 28.572 (3.2%) 377 / 14.434 (2.6%) 547 / 14.138 (3.9%)
    3 17 / 28.572 (<0.1%) 4 / 14.434 (<0.1%) 13 / 14.138 (<0.1%)
    N missing (% missing) 1.214 / 29.786 (4.1%) 271 / 14.705 (1.8%) 943 / 15.081 (6.3%)
Pregnancy > 22 weeks 6.312 / 29.786 (21%) 2.609 / 14.705 (18%) 3.703 / 15.081 (25%)
    N missing (% missing) 0 / 29.786 (0%) 0 / 14.705 (0%) 0 / 15.081 (0%)
Successful birth (at least 1 newborn) 4.736 / 29.786 (16%) 1.892 / 14.705 (13%) 2.844 / 15.081 (19%)
    N missing (% missing) 0 / 29.786 (0%) 0 / 14.705 (0%) 0 / 15.081 (0%)
N° of newborns


    1 4.023 / 4.687 (86%) 1.624 / 1.877 (87%) 2.399 / 2.810 (85%)
    2 652 / 4.687 (14%) 248 / 1.877 (13%) 404 / 2.810 (14%)
    3 12 / 4.687 (0.3%) 5 / 1.877 (0.3%) 7 / 2.810 (0.2%)
    N missing (% missing) 25.099 / 29.786 (84%) 12.828 / 14.705 (87%) 12.271 / 15.081 (81%)
OHSS/Risk OHSS 1.332 / 29.786 (4.5%) 635 / 14.705 (4.3%) 697 / 15.081 (4.6%)
    N missing (% missing) 0 / 29.786 (0%) 0 / 14.705 (0%) 0 / 15.081 (0%)
Severe OHSS 5 / 29.786 (<0.1%) 5 / 14.705 (<0.1%) 0 / 15.081 (0%)
    N missing (% missing) 0 / 29.786 (0%) 0 / 14.705 (0%) 0 / 15.081 (0%)
Ectopic pregnancy 80 / 29.786 (0.3%) 35 / 14.705 (0.2%) 45 / 15.081 (0.3%)
    N missing (% missing) 0 / 29.786 (0%) 0 / 14.705 (0%) 0 / 15.081 (0%)
Miscarriage 1.576 / 29.786 (5.3%) 717 / 14.705 (4.9%) 859 / 15.081 (5.7%)
    N missing (% missing) 0 / 29.786 (0%) 0 / 14.705 (0%) 0 / 15.081 (0%)
1 n / N (%)
Outcomes: Not-interrupted stimulated cycles
Overall, N = 21.1551 Gn used for stimulation
hMg, N = 9.8651 Pergoveris, N = 11.2901
LPS support 16.737 / 21.155 (79%) 7.357 / 9.865 (75%) 9.380 / 11.290 (83%)
    N missing (% missing) 0 / 21.155 (0%) 0 / 9.865 (0%) 0 / 11.290 (0%)
Method of fertilization


    ICSI 15.127 / 21.155 (72%) 7.161 / 9.865 (73%) 7.966 / 11.290 (71%)
    IVF 5.247 / 21.155 (25%) 2.496 / 9.865 (25%) 2.751 / 11.290 (24%)
    Both 781 / 21.155 (3.7%) 208 / 9.865 (2.1%) 573 / 11.290 (5.1%)
    N missing (% missing) 0 / 21.155 (0%) 0 / 9.865 (0%) 0 / 11.290 (0%)
N° oocytes retrieved


    N(% not missing) 21.155(100%) 9.865(100%) 11.290(100%)
    Median (25%-75%) 7.0 (4.0-11.0) 6.0 (3.0-9.0) 8.0 (5.0-13.0)
    Range 1.0, 76.0 1.0, 48.0 1.0, 76.0
    Mean (SD) 8.3 (5.5) 6.9 (4.5) 9.5 (6.0)
    N missing (% missing) 0 (0%) 0 (0%) 0 (0%)
N° of M2 oocytes


    N(% not missing) 21.155(100%) 9.865(100%) 11.290(100%)
    Median (25%-75%) 3.0 (0.0-7.0) 3.0 (1.0-6.0) 3.0 (0.0-7.0)
    Range 0.0, 37.0 0.0, 33.0 0.0, 37.0
    Mean (SD) 4.2 (4.3) 4.1 (3.8) 4.3 (4.7)
    N missing (% missing) 0 (0%) 0 (0%) 0 (0%)
N° of 2PN


    N(% not missing) 21.155(100%) 9.865(100%) 11.290(100%)
    Median (25%-75%) 4.0 (2.0-6.0) 3.0 (2.0-5.0) 4.0 (2.0-7.0)
    Range 0.0, 44.0 0.0, 27.0 0.0, 44.0
    Mean (SD) 4.5 (3.4) 3.7 (2.6) 5.2 (3.8)
    N missing (% missing) 0 (0%) 0 (0%) 0 (0%)
N° embryos cryopreserved


    0 15.592 / 21.155 (74%) 7.568 / 9.865 (77%) 8.024 / 11.290 (71%)
    1 2.619 / 21.155 (12%) 1.213 / 9.865 (12%) 1.406 / 11.290 (12%)
    2 1.725 / 21.155 (8.2%) 662 / 9.865 (6.7%) 1.063 / 11.290 (9.4%)
    ≥3 1.219 / 21.155 (5.8%) 422 / 9.865 (4.3%) 797 / 11.290 (7.1%)
    N missing (% missing) 0 / 21.155 (0%) 0 / 9.865 (0%) 0 / 11.290 (0%)
N° oocytes cryopreserved


    0 21.027 / 21.155 (99%) 9.752 / 9.865 (99%) 11.275 / 11.290 (100%)
    ≥1 128 / 21.155 (0.6%) 113 / 9.865 (1.1%) 15 / 11.290 (0.1%)
    N missing (% missing) 0 / 21.155 (0%) 0 / 9.865 (0%) 0 / 11.290 (0%)
N° of transfered embryos


    1 9.874 / 20.124 (49%) 4.937 / 9.762 (51%) 4.937 / 10.362 (48%)
    2 9.668 / 20.124 (48%) 4.497 / 9.762 (46%) 5.171 / 10.362 (50%)
    3 581 / 20.124 (2.9%) 327 / 9.762 (3.3%) 254 / 10.362 (2.5%)
    4 1 / 20.124 (<0.1%) 1 / 9.762 (<0.1%) 0 / 10.362 (0%)
    N missing (% missing) 1.031 / 21.155 (4.9%) 103 / 9.865 (1.0%) 928 / 11.290 (8.2%)
Stage of embryo development at transfer


    D5 8.001 / 20.116 (40%) 2.551 / 9.755 (26%) 5.450 / 10.361 (53%)
    D3 7.676 / 20.116 (38%) 4.564 / 9.755 (47%) 3.112 / 10.361 (30%)
    D2 3.705 / 20.116 (18%) 2.435 / 9.755 (25%) 1.270 / 10.361 (12%)
    D4 637 / 20.116 (3.2%) 148 / 9.755 (1.5%) 489 / 10.361 (4.7%)
    D6 97 / 20.116 (0.5%) 57 / 9.755 (0.6%) 40 / 10.361 (0.4%)
    N missing (% missing) 1.039 / 21.155 (4.9%) 110 / 9.865 (1.1%) 929 / 11.290 (8.2%)
N° of gestional sacs


    0 13.714 / 19.958 (69%) 7.032 / 9.610 (73%) 6.682 / 10.348 (65%)
    1 5.303 / 19.958 (27%) 2.197 / 9.610 (23%) 3.106 / 10.348 (30%)
    2 924 / 19.958 (4.6%) 377 / 9.610 (3.9%) 547 / 10.348 (5.3%)
    3 17 / 19.958 (<0.1%) 4 / 9.610 (<0.1%) 13 / 10.348 (0.1%)
    N missing (% missing) 1.197 / 21.155 (5.7%) 255 / 9.865 (2.6%) 942 / 11.290 (8.3%)
Pregnancy > 22 weeks 6.311 / 21.155 (30%) 2.609 / 9.865 (26%) 3.702 / 11.290 (33%)
    N missing (% missing) 0 / 21.155 (0%) 0 / 9.865 (0%) 0 / 11.290 (0%)
Successful birth (at least 1 newborn) 4.735 / 21.155 (22%) 1.892 / 9.865 (19%) 2.843 / 11.290 (25%)
    N missing (% missing) 0 / 21.155 (0%) 0 / 9.865 (0%) 0 / 11.290 (0%)
N° of newborns


    1 4.022 / 4.686 (86%) 1.624 / 1.877 (87%) 2.398 / 2.809 (85%)
    2 652 / 4.686 (14%) 248 / 1.877 (13%) 404 / 2.809 (14%)
    3 12 / 4.686 (0.3%) 5 / 1.877 (0.3%) 7 / 2.809 (0.2%)
    N missing (% missing) 16.469 / 21.155 (78%) 7.988 / 9.865 (81%) 8.481 / 11.290 (75%)
OHSS/Risk OHSS 0 / 21.155 (0%) 0 / 9.865 (0%) 0 / 11.290 (0%)
    N missing (% missing) 0 / 21.155 (0%) 0 / 9.865 (0%) 0 / 11.290 (0%)
Severe OHSS 3 / 21.155 (<0.1%) 3 / 9.865 (<0.1%) 0 / 11.290 (0%)
    N missing (% missing) 0 / 21.155 (0%) 0 / 9.865 (0%) 0 / 11.290 (0%)
Ectopic pregnancy 80 / 21.155 (0.4%) 35 / 9.865 (0.4%) 45 / 11.290 (0.4%)
    N missing (% missing) 0 / 21.155 (0%) 0 / 9.865 (0%) 0 / 11.290 (0%)
Miscarriage 1.576 / 21.155 (7.4%) 717 / 9.865 (7.3%) 859 / 11.290 (7.6%)
    N missing (% missing) 0 / 21.155 (0%) 0 / 9.865 (0%) 0 / 11.290 (0%)
1 n / N (%)

5 Outcomes: Frozen thawed embryo transfers - 1° FET cycle

Outcomes: 1° FET cycles
Overall, N = 8.0571 Gn used for stimulation
hMg, N = 3.2351 Pergoveris, N = 4.8221
N° of thawed embyros


    N (% not missing) 5.511 (68%) 2.764 (85%) 2.747 (57%)
    Median (25%-75%) 1.00 (1.00-1.00) 1.00 (1.00-1.00) 1.00 (1.00-2.00)
    Range 0.00, 15.00 0.00, 12.00 0.00, 15.00
    Mean (SD) 1.31 (1.03) 1.35 (1.32) 1.28 (0.60)
    N missing (% missing) 2.546 (32%) 471 (15%) 2.075 (43%)
N° of thawed ovo


    0 7.939 / 8.057 (99%) 3.131 / 3.235 (97%) 4.808 / 4.822 (100%)
    ≥1 118 / 8.057 (1.5%) 104 / 3.235 (3.2%) 14 / 4.822 (0.3%)
N° of transfered embryos


    1 5.304 / 7.823 (68%) 2.461 / 3.197 (77%) 2.843 / 4.626 (61%)
    2 2.305 / 7.823 (29%) 663 / 3.197 (21%) 1.642 / 4.626 (35%)
    0 135 / 7.823 (1.7%) 39 / 3.197 (1.2%) 96 / 4.626 (2.1%)
    3 79 / 7.823 (1.0%) 34 / 3.197 (1.1%) 45 / 4.626 (1.0%)
    N missing (% missing) 234 / 8.057 (2.9%) 38 / 3.235 (1.2%) 196 / 4.822 (4.1%)
Stage of embryo development at transfer


    D5 1.077 / 2.298 (47%) 997 / 2.146 (46%) 80 / 152 (53%)
    D6 593 / 2.298 (26%) 545 / 2.146 (25%) 48 / 152 (32%)
    D3 494 / 2.298 (21%) 476 / 2.146 (22%) 18 / 152 (12%)
    D2 126 / 2.298 (5.5%) 122 / 2.146 (5.7%) 4 / 152 (2.6%)
    D4 8 / 2.298 (0.3%) 6 / 2.146 (0.3%) 2 / 152 (1.3%)
    N missing (% missing) 5.759 / 8.057 (71%) 1.089 / 3.235 (34%) 4.670 / 4.822 (97%)
PGT-A 1 / 8.055 (<0.1%) 1 / 3.233 (<0.1%) 0 / 4.822 (0%)
    N missing (% missing) 2 / 8.057 (<0.1%) 2 / 3.235 (<0.1%) 0 / 4.822 (0%)
N° of gestional sacs


    0 5.265 / 7.882 (67%) 2.231 / 3.157 (71%) 3.034 / 4.725 (64%)
    1 2.374 / 7.882 (30%) 868 / 3.157 (27%) 1.506 / 4.725 (32%)
    2 234 / 7.882 (3.0%) 56 / 3.157 (1.8%) 178 / 4.725 (3.8%)
    3 9 / 7.882 (0.1%) 2 / 3.157 (<0.1%) 7 / 4.725 (0.1%)
    N missing (% missing) 175 / 8.057 (2.2%) 78 / 3.235 (2.4%) 97 / 4.822 (2.0%)
Pregnancy > 22 weeks 2.630 / 8.057 (33%) 931 / 3.235 (29%) 1.699 / 4.822 (35%)
    N missing (% missing) 0 / 8.057 (0%) 0 / 3.235 (0%) 0 / 4.822 (0%)
Successful birth (at least 1 newborn) 1.782 / 8.057 (22%) 618 / 3.235 (19%) 1.164 / 4.822 (24%)
    N missing (% missing) 0 / 8.057 (0%) 0 / 3.235 (0%) 0 / 4.822 (0%)
N° of newborns


    1 1.593 / 1.769 (90%) 578 / 616 (94%) 1.015 / 1.153 (88%)
    2 169 / 1.769 (9.6%) 35 / 616 (5.7%) 134 / 1.153 (12%)
    3 7 / 1.769 (0.4%) 3 / 616 (0.5%) 4 / 1.153 (0.3%)
    N missing (% missing) 6.288 / 8.057 (78%) 2.619 / 3.235 (81%) 3.669 / 4.822 (76%)
1 n / N (%)

6 Outcomes: Frozen thawed embryo transfers - 2° FET cycle

Outcomes: 2° FET cycles
Overall, N = 2.7771 Gn used for stimulation
hMg, N = 1.0241 Pergoveris, N = 1.7531
N° of thawed embyros


    1 1.531 / 1.818 (84%) 796 / 914 (87%) 735 / 904 (81%)
    2 218 / 1.818 (12%) 65 / 914 (7.1%) 153 / 904 (17%)
    0 49 / 1.818 (2.7%) 44 / 914 (4.8%) 5 / 904 (0.6%)
    3 18 / 1.818 (1.0%) 8 / 914 (0.9%) 10 / 904 (1.1%)
    4 2 / 1.818 (0.1%) 1 / 914 (0.1%) 1 / 904 (0.1%)
N° of thawed ovo


    0 2.728 / 2.777 (98%) 980 / 1.024 (96%) 1.748 / 1.753 (100%)
    ≥1 49 / 2.777 (1.8%) 44 / 1.024 (4.3%) 5 / 1.753 (0.3%)
N° of transfered embryos


    1 1.935 / 2.716 (71%) 883 / 1.017 (87%) 1.052 / 1.699 (62%)
    2 719 / 2.716 (26%) 118 / 1.017 (12%) 601 / 1.699 (35%)
    0 36 / 2.716 (1.3%) 11 / 1.017 (1.1%) 25 / 1.699 (1.5%)
    3 26 / 2.716 (1.0%) 5 / 1.017 (0.5%) 21 / 1.699 (1.2%)
    N missing (% missing) 61 / 2.777 (2.2%) 7 / 1.024 (0.7%) 54 / 1.753 (3.1%)
Stage of embryo development at transfer


    D5 420 / 828 (51%) 389 / 764 (51%) 31 / 64 (48%)
    D6 249 / 828 (30%) 225 / 764 (29%) 24 / 64 (38%)
    D3 143 / 828 (17%) 135 / 764 (18%) 8 / 64 (13%)
    D2 12 / 828 (1.4%) 11 / 764 (1.4%) 1 / 64 (1.6%)
    D4 4 / 828 (0.5%) 4 / 764 (0.5%) 0 / 64 (0%)
    N missing (% missing) 1.949 / 2.777 (70%) 260 / 1.024 (25%) 1.689 / 1.753 (96%)
PGT-A 1 / 2.776 (<0.1%) 1 / 1.024 (<0.1%) 0 / 1.752 (0%)
    N missing (% missing) 1 / 2.777 (<0.1%) 0 / 1.024 (0%) 1 / 1.753 (<0.1%)
N° of gestional sacs


    0 1.875 / 2.730 (69%) 728 / 990 (74%) 1.147 / 1.740 (66%)
    1 789 / 2.730 (29%) 248 / 990 (25%) 541 / 1.740 (31%)
    2 65 / 2.730 (2.4%) 14 / 990 (1.4%) 51 / 1.740 (2.9%)
    3 1 / 2.730 (<0.1%) 0 / 990 (0%) 1 / 1.740 (<0.1%)
    N missing (% missing) 47 / 2.777 (1.7%) 34 / 1.024 (3.3%) 13 / 1.753 (0.7%)
Pregnancy > 22 weeks 857 / 2.777 (31%) 264 / 1.024 (26%) 593 / 1.753 (34%)
    N missing (% missing) 0 / 2.777 (0%) 0 / 1.024 (0%) 0 / 1.753 (0%)
Successful birth (at least 1 newborn) 563 / 2.777 (20%) 173 / 1.024 (17%) 390 / 1.753 (22%)
    N missing (% missing) 0 / 2.777 (0%) 0 / 1.024 (0%) 0 / 1.753 (0%)
N° of newborns


    1 507 / 555 (91%) 162 / 172 (94%) 345 / 383 (90%)
    2 48 / 555 (8.6%) 10 / 172 (5.8%) 38 / 383 (9.9%)
    N missing (% missing) 2.222 / 2.777 (80%) 852 / 1.024 (83%) 1.370 / 1.753 (78%)
1 n / N (%)

7 Outcomes: Frozen thawed embryo transfers - 3° FET cycle

Outcomes: 3° FET cycles
Overall, N = 8481 Gn used for stimulation
hMg, N = 3391 Pergoveris, N = 5091
N° of thawed embyros


    1 446 / 542 (82%) 256 / 307 (83%) 190 / 235 (81%)
    2 62 / 542 (11%) 21 / 307 (6.8%) 41 / 235 (17%)
    0 33 / 542 (6.1%) 30 / 307 (9.8%) 3 / 235 (1.3%)
    3 1 / 542 (0.2%) 0 / 307 (0%) 1 / 235 (0.4%)
N° of thawed ovo


    0 815 / 848 (96%) 309 / 339 (91%) 506 / 509 (99%)
    ≥1 33 / 848 (3.9%) 30 / 339 (8.8%) 3 / 509 (0.6%)
N° of transfered embryos


    1 594 / 836 (71%) 290 / 337 (86%) 304 / 499 (61%)
    2 224 / 836 (27%) 39 / 337 (12%) 185 / 499 (37%)
    0 11 / 836 (1.3%) 7 / 337 (2.1%) 4 / 499 (0.8%)
    3 7 / 836 (0.8%) 1 / 337 (0.3%) 6 / 499 (1.2%)
    N missing (% missing) 12 / 848 (1.4%) 2 / 339 (0.6%) 10 / 509 (2.0%)
Stage of embryo development at transfer


    D5 142 / 298 (48%) 133 / 278 (48%) 9 / 20 (45%)
    D6 104 / 298 (35%) 96 / 278 (35%) 8 / 20 (40%)
    D3 46 / 298 (15%) 44 / 278 (16%) 2 / 20 (10%)
    D2 3 / 298 (1.0%) 3 / 278 (1.1%) 0 / 20 (0%)
    D4 3 / 298 (1.0%) 2 / 278 (0.7%) 1 / 20 (5.0%)
    N missing (% missing) 550 / 848 (65%) 61 / 339 (18%) 489 / 509 (96%)
PGT-A 1 / 848 (0.1%) 1 / 339 (0.3%) 0 / 509 (0%)
    N missing (% missing) 0 / 848 (0%) 0 / 339 (0%) 0 / 509 (0%)
N° of gestional sacs


    0 592 / 836 (71%) 253 / 330 (77%) 339 / 506 (67%)
    1 229 / 836 (27%) 76 / 330 (23%) 153 / 506 (30%)
    2 15 / 836 (1.8%) 1 / 330 (0.3%) 14 / 506 (2.8%)
    N missing (% missing) 12 / 848 (1.4%) 9 / 339 (2.7%) 3 / 509 (0.6%)
Pregnancy > 22 weeks 247 / 848 (29%) 78 / 339 (23%) 169 / 509 (33%)
    N missing (% missing) 0 / 848 (0%) 0 / 339 (0%) 0 / 509 (0%)
Successful birth (at least 1 newborn) 160 / 848 (19%) 52 / 339 (15%) 108 / 509 (21%)
    N missing (% missing) 0 / 848 (0%) 0 / 339 (0%) 0 / 509 (0%)
N° of newborns


    1 142 / 156 (91%) 50 / 50 (100%) 92 / 106 (87%)
    2 14 / 156 (9.0%) 0 / 50 (0%) 14 / 106 (13%)
    N missing (% missing) 692 / 848 (82%) 289 / 339 (85%) 403 / 509 (79%)
1 n / N (%)

8 Outcomes: Frozen thawed embryo transfers - 4-6° FET cycles

Outcomes: 4-6° FET cycles
Overall, N = 3111 Gn used for stimulation
hMg, N = 1631 Pergoveris, N = 1481
N° of thawed embyros


    1 183 / 223 (82%) 125 / 149 (84%) 58 / 74 (78%)
    0 21 / 223 (9.4%) 20 / 149 (13%) 1 / 74 (1.4%)
    2 18 / 223 (8.1%) 4 / 149 (2.7%) 14 / 74 (19%)
    3 1 / 223 (0.4%) 0 / 149 (0%) 1 / 74 (1.4%)
N° of thawed ovo


    0 290 / 311 (93%) 143 / 163 (88%) 147 / 148 (99%)
    ≥1 21 / 311 (6.8%) 20 / 163 (12%) 1 / 148 (0.7%)
N° of transfered embryos


    1 240 / 305 (79%) 145 / 160 (91%) 95 / 145 (66%)
    2 57 / 305 (19%) 11 / 160 (6.9%) 46 / 145 (32%)
    0 6 / 305 (2.0%) 3 / 160 (1.9%) 3 / 145 (2.1%)
    3 2 / 305 (0.7%) 1 / 160 (0.6%) 1 / 145 (0.7%)
    N missing (% missing) 6 / 311 (1.9%) 3 / 163 (1.8%) 3 / 148 (2.0%)
Stage of embryo development at transfer


    D5 64 / 150 (43%) 58 / 140 (41%) 6 / 10 (60%)
    D6 58 / 150 (39%) 55 / 140 (39%) 3 / 10 (30%)
    D3 25 / 150 (17%) 25 / 140 (18%) 0 / 10 (0%)
    D4 2 / 150 (1.3%) 1 / 140 (0.7%) 1 / 10 (10%)
    D2 1 / 150 (0.7%) 1 / 140 (0.7%) 0 / 10 (0%)
    N missing (% missing) 161 / 311 (52%) 23 / 163 (14%) 138 / 148 (93%)
PGT-A 0 / 311 (0%) 0 / 163 (0%) 0 / 148 (0%)
    N missing (% missing) 0 / 311 (0%) 0 / 163 (0%) 0 / 148 (0%)
N° of gestional sacs


    0 224 / 305 (73%) 121 / 158 (77%) 103 / 147 (70%)
    1 79 / 305 (26%) 37 / 158 (23%) 42 / 147 (29%)
    2 2 / 305 (0.7%) 0 / 158 (0%) 2 / 147 (1.4%)
    N missing (% missing) 6 / 311 (1.9%) 5 / 163 (3.1%) 1 / 148 (0.7%)
Pregnancy > 22 weeks 82 / 311 (26%) 37 / 163 (23%) 45 / 148 (30%)
    N missing (% missing) 0 / 311 (0%) 0 / 163 (0%) 0 / 148 (0%)
Successful birth (at least 1 newborn) 48 / 311 (15%) 18 / 163 (11%) 30 / 148 (20%)
    N missing (% missing) 0 / 311 (0%) 0 / 163 (0%) 0 / 148 (0%)
N° of newborns


    1 45 / 47 (96%) 18 / 18 (100%) 27 / 29 (93%)
    2 2 / 47 (4.3%) 0 / 18 (0%) 2 / 29 (6.9%)
    N missing (% missing) 264 / 311 (85%) 145 / 163 (89%) 119 / 148 (80%)
1 n / N (%)

9 Cumulative outcomes

For cumulative outcomes, the following criteria have been applied:

  • If the number of cycles is equal to one for a “block” (i.e., only the stimulation cycle is present) and both the number of oocytes cryopreserved and the embryos cryopreserved is equal to 0, then the cycle is considered Fresh transfer only. To be more precise, this is to be intended as intention to fresh transfer only, because the totality of stimulated cycles with no further usage and no cryoconservation have been included, even if the cycle was interrupted (e.g., no transfer because of medical reasons during the stimulation process; technically we are considering the interruption of the cycle as a failure and the absence of embrio-transfer as it would have been a cycle with regular transfer and a negative outcome).

  • If the number of cycles is equal to 2 or more (with only 1 stimulated cycle and 1 or multiple thawing cycles), or if the number of cycles is equal to 1 but with simultaneous cryopreservation, then that cycle/ series of cycles have been labelled as Fresh/No fresh + frozen ovo/embryo ± thawing. The choice to include all the stimulated cycles that have no further usage of ooyctes (no thawing cycles) but with cryopreservation is based on the fact that the cryoperservation highlights a more favorable cycle ( and the cryopreservation itself represented the confirmation) and we do not see any furhter cycle because more oocytes retrieved – > more oocytes cryo & more favourable oocytes selected.

9.1 Outcomes: Fresh transfer only vs Fresh/No fresh + frozen ovo/embryo ± thawing - cumulative outcomes for Pergoveris

Cumulative outcomes for Pergoveris, intention to treat
Overall, N = 15.0811 Type of transfer
No cryo, intention to treat, N = 9.0461 Cryo ± Fresh/No fresh ET ± thawing, N = 6.0351
Cumulative pregnancy > 22 weeks 5.577 (37%) 1.974 (22%) 3.603 (60%)
Cumulative live birth 4.352 (29%) 1.493 (17%) 2.859 (47%)
1 n (%)

As expected, the overall (N = 15.081) from the table above is equal to the number of stimulated cycles with Pergoveris.

In fact, we can consider 15.081 as the number of women (given that we identify a woman as a single stimulation cycle ± thawing cycles) that underwent at least one cycle. In other words, out of 15.081 first stimulation cycles, 9.046 were not followed by any other cycle while 6.035 were followed by at least 1 thwaing cycle and with a total of 7.233 thawing cycles: 9.046 stimulation cycles with no following + 6.035 stimulation cycles followed by additional 7.233 thawing cycles = 22.341 cycles where Pergoveris was the drug chosen for the stimulation cycle.

The same is applicable for hMg coohrt, which is given in the following table.

9.2 Outcomes: Fresh transfer only vs Fresh/No fresh + frozen ovo/embryo ± thawing - cumulative outcomes for hMg

Cumulative outcomes for hMg, intention to treat
Overall, N = 14.7051 Type of transfer
No cryo, intention to treat, N = 10.6881 Cryo ± Fresh/No fresh ET ± thawing, N = 4.0171
Cumulative pregnancy > 22 weeks 3.609 (25%) 1.676 (16%) 1.933 (48%)
Cumulative live birth 2.645 (18%) 1.168 (11%) 1.477 (37%)
1 n (%)

9.3 Outcomes: Fresh transfer only vs Fresh/No fresh + frozen ovo/embryo ± thawing - cumulative outcomes for hMg

The same outcomes are reported with a further separation in stimulated cycles, both for Pergoveris and hMg. In this case, the number of cycles with cryopreservation is the same, but the cycles composed by stimulation cycle with no cryopreservation is further divided in cycles that effectively went to ET vs cycles that were cancelled before ET, for whatever reason.

Cumulative outcomes for Pergoveris
Overall, N = 15.0811 Type of transfer
No cryo, no fresh ET, N = 2.2701 No cryo, fresh ET, N = 6.7761 Cryo ± Fresh/No fresh ET ± thawing, N = 6.0351
Clinical pregnancy > 22 weeks 5.576 (37%) 0 (0%) 1.973 (29%) 3.603 (60%)
Cumulative live birth 4.351 (29%) 0 (0%) 1.492 (22%) 2.859 (47%)
1 n (%)
Cumulative outcomes for hMg
Overall, N = 14.7051 Type of transfer
No cryo, no fresh ET, N = 3.3901 No cryo, fresh ET, N = 7.2981 Cryo ± Fresh/No fresh ET ± thawing, N = 4.0171
Cumulative pregnancy > 22 weeks 3.609 (25%) 0 (0%) 1.676 (23%) 1.933 (48%)
Cumulative live birth 2.645 (18%) 0 (0%) 1.168 (16%) 1.477 (37%)
1 n (%)

10 Number of cycles with no missing data

Considering full information about the following variables:

  • Diagnosis

  • AMH levels

  • Age

  • BMI

  • Total dose of GnRH analog (No info about initial dose)

  • Drug used for final ooctye maturation triggering

  • N° of ooyctes recovered

  • Presence of clinical pregnancy

  • Birth of at least one liveborn

Out of 41.783 cycles, 18.607 cycles are complete. If we consider the same subset of variables with the exception of AMH, 32.723 complete cycles can be identified.

11 Continuous variables ditribution

Finally, we provide the histogram of numeric variables to display their distribution.

Each variable distribution is represented for both drugs in the same graph to highlight distribution differences/similarities.