Utility of Deferred Embryo Transfer in an In Vitro Program With Single Embryo Transfer Policy
Phase: NA
Conditions: Single Embryo Transfer, Embryo Implantation, Delayed, Pregnancy Rate
Sponsor: University Hospital Virgen de las Nieves

Study‌ ‌Protocol‌ ‌and‌ ‌Statistical‌ ‌Analysis‌ ‌Plan‌ ‌
 
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Analysis‌ ‌of‌ ‌the‌ ‌utility‌ ‌of‌ ‌freeze-all‌ ‌strategy‌ ‌in‌ ‌an‌ ‌In‌ ‌Vitro‌‌
 
 
 
 
 
 
 
 
 
 
 
Fertilization‌ ‌program‌ ‌with‌ ‌single‌ ‌embryo‌ ‌transfer‌ ‌policy.‌ ‌
 
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NCT‌ ‌number:‌ ‌PI-0353-2016‌ ‌
 
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10th‌ ‌October‌ ‌2016‌ ‌
 
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STUDY‌ ‌PROTOCOL:‌ ‌
 
‌
 
The‌‌study‌‌was‌‌designed‌‌as‌‌a‌‌prospective,‌‌randomized,‌‌two-arm,‌‌parallel,‌‌unblinded‌‌
 
 
 
 
   
 
 
 
 
 
study,‌ ‌during‌ ‌which‌ ‌We‌ ‌will‌ ‌include‌ ‌138‌ ‌couples‌ ‌(69‌ ‌in‌‌each‌‌group)‌‌of‌‌IVF‌‌/‌‌ICSI‌‌
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
users.‌ ‌Cycles‌ ‌canceled‌ ‌or‌ ‌without‌ ‌transfer‌ ‌(either‌ ‌due‌ ‌to‌ ‌not‌ ‌obtaining‌ ‌oocytes,‌‌
 
 
 
 
 
 
 
 
 
 
 
 
non-fertilization‌‌or‌‌arrest‌‌of‌‌embryonic‌‌development)‌‌will‌‌not‌‌be‌‌included‌‌in‌‌the‌‌study.‌‌
 
 
 
 
 
 
 
 
 
   
 
 
The‌‌assignment‌‌of‌‌the‌‌pairs‌‌to‌‌each‌‌of‌‌the‌‌groups‌‌will‌‌be‌‌carried‌‌out‌‌by‌‌means‌‌of‌‌a‌‌
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
random‌ ‌sampling‌ ‌procedure.‌ ‌The‌ ‌randomization‌ ‌list‌‌will‌‌be‌‌created‌‌specifically‌‌for‌‌
 
 
 
 
 
 
 
 
 
 
 
this‌ ‌project‌ ‌and‌ ‌will‌ ‌be‌ ‌guarded‌ ‌by‌ ‌an‌ ‌outsider‌ ‌to‌ ‌the‌ ‌research‌ ‌team:‌ ‌
 
‌
 
-Group‌‌I‌‌(experimental):‌‌fresh‌‌transfer‌‌is‌‌not‌‌performed,‌‌the‌‌best‌‌quality‌‌embryo‌‌is‌‌
   
 
 
 
 
 
 
 
 
 
   
cryopreserved.‌ ‌Elective‌ ‌transfer‌ ‌in‌ ‌a‌ ‌later‌ ‌cycle‌ ‌of‌ ‌the‌ ‌cryopreserved‌ ‌embryo.‌ ‌
 
-Group‌ ‌II‌ ‌(control):‌ ‌fresh‌ ‌transfer‌ ‌of‌ ‌the‌ ‌best‌ ‌quality‌ ‌embryo.‌ ‌
 
‌
 
Couples‌‌will‌‌be‌‌able‌‌to‌‌participate‌‌in‌‌the‌‌study‌‌for‌‌only‌‌one‌‌cycle.‌‌Each‌‌couple‌‌will‌‌be‌‌
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
interviewed‌‌by‌‌a‌‌member‌‌of‌‌the‌‌team‌‌who‌‌will‌‌explain‌‌the‌‌characteristics‌‌of‌‌the‌‌study‌‌
 
   
 
 
 
 
 
 
 
 
 
 
 
 
and‌ ‌they‌ ‌will‌ ‌be‌ ‌given‌ ‌an‌ ‌Information‌ ‌Sheet.‌ ‌It‌ ‌is‌ ‌necessary‌ ‌to‌ ‌obtain‌‌the‌‌written‌‌
 
 
 
 
 
 
 
   
 
 
 
 
 
 
informed‌‌consent‌‌of‌‌each‌‌couple.‌‌The‌‌person‌‌outside‌‌the‌‌investigation‌‌team‌‌who‌‌is‌‌
 
 
 
 
 
 
 
 
 
 
 
   
guarding‌ ‌the‌ ‌randomization‌ ‌list‌ ‌will‌ ‌assign‌ ‌the‌ ‌corresponding‌ ‌treatment‌ ‌group.‌ ‌
 
‌
 
Before‌‌starting‌‌the‌‌study,‌‌ethical‌‌approval‌‌will‌‌be‌‌processed‌‌by‌‌the‌‌Ethics‌‌Committee‌‌
 
 
 
 
 
 
 
 
 
 
 
 
 
through‌ ‌the‌ ‌Ethics‌ ‌Portal‌ ‌of‌ ‌the‌ ‌Biomedical‌ ‌Research‌ ‌of‌ ‌Andalusia.‌ ‌
 
‌
 
Patients‌ ‌must‌ ‌follow‌ ‌ovulation‌ ‌stimulating‌ ‌treatment,‌ ‌in‌ ‌order‌ ‌to‌ ‌achieve‌ ‌multiple‌‌
 
 
 
 
 
 
 
 
 
 
 
follicular‌ ‌development.‌ ‌A‌ ‌"long‌ ‌analog"‌ ‌GnRH‌ ‌agonist‌ ‌protocol‌ ‌will‌ ‌be‌ ‌used.‌ ‌This‌‌
 
 
 
 
 
 
 
 
 
 
 
 
consists‌‌of‌‌administering‌‌from‌‌the‌‌day‌‌22‌‌of‌‌the‌‌cycle‌‌0.1‌‌mg‌‌/‌‌day‌‌of‌‌GnRH‌‌analog‌‌
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
(Decapeptyl‌ ‌0.1;‌ ‌Lasa,‌ ‌Barcelona,‌ ‌​Spain)‌ ‌until‌ ‌the‌ ‌day‌ ‌the‌ ‌gonadotropin‌‌
 
 
 
 
 
 
 
 
 
 
administration,‌‌in‌‌which‌‌the‌‌dose‌‌is‌‌reduced‌‌to‌‌50%‌‌until‌‌the‌‌day‌‌of‌‌hCG.‌‌After‌‌10-14‌‌
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
days‌‌of‌‌administration‌‌of‌‌the‌‌agonist,‌‌we‌‌proceed‌‌to‌‌check‌‌the‌‌pituitary‌‌braking‌‌by‌‌
 
 
 
 
 
 
 
 
 
 
 
 
 
 
means‌‌of‌‌ovarian‌‌vaginal‌‌ultrasound‌‌(absence‌‌of‌‌follicles‌‌and‌‌cysts).‌‌Then,‌‌300‌‌IU‌‌of‌‌
 
 
 
 
 
 
 
 
 
 
 
 
 
 
recombinant‌‌FSH‌‌(rFSH)‌‌is‌‌administered‌‌per‌‌day‌‌(Gonal‌‌F,‌‌Merck,‌‌Madrid,‌‌Spain)‌‌for‌‌
 
 
   
 
 
 
   
 
 
 
 
two‌‌days,‌‌and‌‌150‌‌IU‌‌of‌‌FSHr‌‌from‌‌the‌‌3rd‌‌to‌‌the‌‌7th‌‌day.‌‌On‌‌this‌‌day,‌‌ultrasound‌‌
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
control‌‌of‌‌the‌‌follicular‌‌development‌‌is‌‌accomplished‌‌in‌‌order‌‌to‌‌re-adjust‌‌the‌‌dose‌‌of‌‌
 
 
 
 
   
   
 
 
 
 
 
 
rFSH‌‌to‌‌each‌‌patient.‌‌Once‌‌the‌‌follicular‌‌response‌‌is‌‌adequate‌‌(more‌‌than‌‌3‌‌ovarian‌‌
 
 
 
 
 
 
 
   
 
 
   
 
follicles‌‌greater‌‌than‌‌18‌‌mm‌‌in‌‌diameter),‌‌we‌‌proceed‌‌to‌‌trigger‌‌ovulation‌‌using‌‌6500‌‌
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IU‌ ‌hCG‌ ‌(Ovitrelle,‌ ‌Merck,‌ ‌Darmstadt,‌ ‌Germany).‌ ‌
 
‌
 
Oocyte‌ ‌retrieval‌ ‌will‌ ‌be‌ ‌performed‌ ‌by‌ ‌transvaginal‌ ‌ultrasound-guided‌ ‌follicular‌‌
 
 
 
 
 
 
 
 
 
puncture‌ ‌36‌ ‌hours‌ ‌after‌ ‌the‌ ‌injection‌ ‌of‌ ‌hCG,‌ ‌anticipating‌ ‌the‌ ‌ovulatory‌ ‌process,‌‌
 
 
 
 
 
 
 
 
 
 
 
 
using‌ ‌an‌ ‌ovarian‌ ‌puncture‌ ‌needle‌ ‌(Labotect‌ ‌LaborTechnik-Göttingen,‌ ‌Göttingen,‌‌
 
 
 
 
 
 
 
 
Germany).‌‌The‌‌follicles‌‌larger‌‌than‌‌17‌‌mm‌‌are‌‌punctured‌‌one‌‌by‌‌one,‌‌aspirating‌‌their‌‌
 
 
 
 
 
 
 
 
 
 
 
 
 
 
content‌ ‌into‌ ‌fluid‌ ‌collection‌ ‌tubes.‌ ‌
 
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The‌‌content‌‌of‌‌the‌‌aspirated‌‌follicle‌‌should‌‌be‌‌transported‌‌quickly‌‌to‌‌the‌‌laboratory‌‌to‌‌
 
 
 
 
 
 
 
 
 
 
 
 
 
 
immediately‌ ‌check‌ ‌for‌ ‌the‌ ‌presence‌ ‌of‌ ‌the‌ ‌cumulus-oocyte‌ ‌complex.‌ ‌Antibiotic‌‌
 
 
 
 
 
 
 
 
 
 
prophylaxis‌‌is‌‌not‌‌routinely‌‌performed,‌‌and‌‌only‌‌in‌‌cases‌‌where‌‌the‌‌puncture‌‌is‌‌more‌‌
   
 
 
 
 
   
 
 
 
   
 
difficult,‌ ‌a‌ ‌single‌ ‌dose‌ ‌of‌ ‌1,500‌ ‌mg‌ ‌of‌ ‌cefuroxime‌ ‌sodium‌ ‌will‌ ‌be‌ ‌administered‌‌
 
 
 
 
 
 
 
 
 
 
 
 
 
intravenously‌‌(Cefuroxime‌‌Normon‌‌EGF,‌‌Madrid,‌‌Spain)‌‌or‌‌1000‌‌mg‌‌of‌‌erythromycin‌‌
 
 
 
 
 
 
 
 
 
 
 
lactobionate‌‌(Pantomycin‌‌Abbot,‌‌Madrid,‌‌Spain)‌‌in‌‌patients‌‌allergic‌‌to‌‌beta-lactams.‌‌
 
 
 
 
 
 
 
 
 
 
Once‌‌the‌‌follicular‌‌fluid‌‌(FF)‌‌arrive‌‌at‌‌the‌‌laboratory,‌‌the‌‌search‌‌and‌‌identification‌‌of‌‌
 
 
 
 
 
 
 
 
 
 
 
 
 
 
the‌
‌cumulus-oocyte‌
‌complexes‌
‌is‌
‌performed‌
‌by‌
‌locating‌
‌them‌
‌under‌‌
 
 
 
 
 
 
 
 
 
stereomicroscopic‌‌vision‌‌in‌‌a‌‌100x15‌‌mm‌‌Petri.‌‌They‌‌are‌‌placed‌‌in‌‌a‌‌new‌‌35x10‌‌mm‌‌
 
 
   
 
 
 
 
 
     
 
 
 
Petri‌ ‌dish‌ ‌inside‌ ‌a‌ ‌few‌ ‌drops‌ ‌of‌ ‌MOPS‌ ‌culture‌ ‌medium‌ ‌Vitrolife‌ ‌(IVF‌ ‌Science‌‌
 
 
 
 
 
 
 
 
 
 
 
 
 
Scandinavia,‌ ‌Gothenburg,‌ ‌Sweden)‌ ‌previously‌ ‌aerated‌ ‌and‌ ‌heated‌ ‌to‌ ‌37ºC,‌ ‌to‌‌
 
 
 
 
 
 
 
 
 
 
eliminate‌ ‌the‌ ‌remains‌ ‌of‌ ‌FF.‌ ‌
 
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IVF/ICSI‌ ‌and‌ ‌embryo‌ ‌culture‌ ‌will‌ ‌then‌ ‌be‌ ‌performed.‌ ‌To‌ ‌perform‌ ‌sperm‌‌
 
 
 
 
 
 
 
 
 
 
 
microinsemination‌‌(ICSI)‌‌it‌‌is‌‌necessary‌‌to‌‌remove‌‌the‌‌cumulus‌‌and‌‌corona‌‌radiata‌‌
 
   
 
 
 
 
 
 
 
 
 
from‌ ‌the‌ ‌oocyte.‌ ‌To‌ ‌decumulate,‌ ‌the‌ ‌crown-oocyte‌ ‌cluster‌ ‌complex‌ ‌is‌ ‌submerged‌ ‌in‌ ‌a‌ ‌
 
solution‌ ‌with‌ ‌80‌ ‌IU‌ ‌/‌ ‌mL‌ ‌hyaluronidase‌ ‌(HYASE,‌ ‌IVF‌ ‌Science‌ ‌Scandinavia,‌‌
 
 
 
   
 
 
 
 
 
 
Gothenburg,‌‌Sweden)‌‌for‌‌10-20‌‌seconds‌‌aspirating‌‌the‌‌complex‌‌several‌‌times‌‌using‌‌
 
 
 
 
 
 
 
 
 
 
 
a‌ ‌pasteur‌ ‌pipette.‌ ‌The‌ ‌microinsemination‌ ‌technique‌ ‌is‌ ‌performed‌ ‌under‌ ‌a‌ ‌microscope‌ ‌
 
inverted‌ ‌with‌ ‌Eppendorf‌ ‌and‌ ‌Narishigue‌ ‌micromanipulators‌ ‌and‌ ‌microinjectors.‌ ‌In‌‌
 
 
 
 
 
 
 
 
 
Vitro‌ ‌Fertilization‌ ‌(IVF)‌ ‌is‌ ‌performed‌ ‌in‌ ‌a‌ ‌five-well‌ ‌plate,‌ ‌depositing‌‌0.5‌‌mL‌‌of‌‌IVF‌‌
 
 
 
 
 
   
 
 
 
 
 
 
 
medium‌‌(Vitrolife,‌‌Sweden)‌‌and‌‌0.5‌‌mL‌‌of‌‌Ovoil‌‌(Vitrolife,‌‌Sweden)‌‌in‌‌each‌‌well.‌‌Five‌‌
 
 
 
 
 
 
 
 
 
   
 
 
 
clusters‌ ‌are‌ ‌left‌ ‌per‌ ‌well‌ ‌and‌ ‌100,000‌ ‌sperm/mL‌ ‌are‌ ‌added.‌ ‌
 
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In‌ ‌both‌ ‌cases,‌ ‌the‌ ‌oocytes‌ ‌are‌ ‌cultured‌ ‌in‌ ‌a‌ ‌Thermo-Fisher‌ ‌incubator,‌ ‌within‌ ‌a‌‌
 
 
 
 
 
 
 
 
 
 
 
 
 
morphokinetic‌ ‌platform‌ ‌(PrimoVision).‌ ‌The‌ ‌following‌ ‌days‌ ‌are‌ ‌evaluated‌ ‌for‌ ‌their‌‌
 
 
 
 
 
 
 
 
 
 
classification,‌ ‌choosing‌ ‌the‌ ‌one‌ ‌of‌ ‌better‌ ‌implantation‌ ‌potential‌ ‌according‌ ‌to‌ ‌the‌‌
 
 
 
 
 
 
 
 
 
 
 
division‌ ‌times‌ ‌measured‌ ‌by‌ ‌morphokinetics‌ ‌and‌ ‌the‌ ‌morphological‌ ‌criteria‌ ‌of‌ ‌the‌‌
 
 
 
 
 
 
 
 
 
 
 
Spanish‌ ‌Association‌ ‌for‌ ‌the‌ ‌Study‌ ‌of‌ ‌Reproduction‌ ‌Biology‌ ‌(ASEBIR)‌‌reviewed‌‌in‌‌
 
 
 
 
 
 
 
 
 
 
 
2015.‌ ‌
 
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The‌‌embryo‌‌transfer‌‌will‌‌be‌‌carried‌‌out‌‌in‌‌group‌‌2‌‌on‌‌the‌‌third‌‌day,‌‌choosing‌‌the‌‌best‌‌
 
 
 
 
 
 
   
   
 
 
 
 
 
 
 
embryo‌‌according‌‌to‌‌the‌‌previous‌‌criteria.‌‌In‌‌Group‌‌1‌‌embryos‌‌will‌‌be‌‌cryopreserved‌‌
 
 
 
 
 
 
 
   
 
 
 
 
by‌ ‌vitrification,‌ ‌selecting‌ ‌the‌ ‌best‌ ‌one‌ ‌for‌ ‌deferred‌ ‌transfer.‌ ‌The‌ ‌commercial‌‌
 
 
 
 
 
 
 
 
 
 
 
vitrification‌ ‌media‌ ‌will‌ ‌be‌ ‌Medicult‌ ‌Vitrification,‌ ‌and‌ ‌the‌ ‌storage‌ ‌device‌ ‌will‌ ‌be‌‌
 
 
 
 
 
 
 
 
 
 
 
 
Cryoleaf‌ ‌(McGill‌ ‌Cryoleaf,‌ ‌Medicult,‌ ‌Denmark).‌ ‌All‌ ‌cryopreserved‌ ‌embryos‌ ‌will‌ ‌be‌‌
 
 
 
 
 
 
 
 
 
 
stored‌‌in‌‌liquid‌‌nitrogen‌‌at‌‌-196ºC‌‌in‌‌storage‌‌cylinders‌‌(Air‌‌Liquide,‌‌France).‌‌The‌‌day‌‌
 
 
 
 
 
 
 
 
 
 
 
 
 
 
before‌ ‌cryotransfer,‌ ‌the‌ ‌embryo‌ ‌is‌ ‌devitrified,‌ ‌using‌ ‌the‌ ‌thawing‌ ‌kit‌ ‌(Medicult‌‌
 
 
 
 
 
 
 
 
 
 
 
Warming,‌‌Denmark).‌‌At‌‌the‌‌end,‌‌the‌‌embryos‌‌are‌‌washed‌‌in‌‌G2‌‌medium‌‌(Vitrolife),‌‌
 
 
 
 
 
 
 
 
 
 
 
 
 
leaving‌ ‌them‌ ‌in‌ ‌cultivation‌ ‌until‌ ‌the‌ ‌following‌ ‌day,‌ ‌after‌ ‌evaluation‌ ‌of‌ ‌embryonic‌‌
 
 
 
 
 
 
 
 
 
 
 
 
quality‌‌and‌‌cryosurvival‌‌(percentage‌‌of‌‌lysed‌‌cells).‌‌The‌‌endometrium‌‌of‌‌the‌‌woman‌‌
 
 
 
 
 
 
 
 
 
 
 
 
is‌ ‌prepared‌ ‌by‌ ‌treatment‌‌with‌‌estradiol‌‌valerate‌‌and‌‌progesterone.‌‌The‌‌day‌‌of‌‌the‌‌
 
 
 
 
 
 
 
 
 
 
 
 
 
cryotransfer‌ ‌embryonic‌‌quality‌‌is‌‌assessed‌‌again,‌‌emphasizing‌‌embryonic‌‌division.‌‌
 
 
 
 
 
 
 
 
 
Cryotransfer‌ ‌is‌ ‌done‌ ‌by‌ ‌the‌ ‌same‌ ‌technique‌ ‌than‌ ‌fresh‌ ‌transfer.‌ ‌
 

Workplan:‌ ‌
 
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First‌ ‌year:‌ ‌
 
-‌ ‌Our‌‌center‌‌is‌‌routinely‌‌able‌‌to‌‌carry‌‌out‌‌the‌‌vitrification,‌‌so‌‌it‌‌is‌‌not‌‌necessary‌‌to‌‌
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
fine-tune‌ ‌our‌ ‌techniques.‌ ‌
 
-‌ ‌Design‌ ‌of‌ ‌the‌ ‌Access‌ ‌database‌ ‌with‌ ‌the‌ ‌variables‌ ‌to‌ ‌be‌ ‌analyzed.‌ ‌
 
-‌ ‌Beginning‌ ‌of‌ ‌the‌ ‌interviews‌ ‌and‌ ‌selection‌ ‌of‌ ‌patients‌ ‌
 
-‌ ‌Beginning‌ ‌of‌ ‌the‌ ‌IVF/ICSI‌ ‌cycles‌ ‌and‌ ‌cryotransfers.‌ ‌
 
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Second‌ ‌year:‌ ‌
 
-‌ ‌Continue‌ ‌with‌ ‌the‌ ‌selection‌ ‌of‌ ‌patients‌ ‌until‌ ‌completing‌ ‌the‌ ‌expected‌ ‌number.‌‌ ‌
  
-‌ ‌Continuation‌ ‌of‌ ‌IVF/ICSI‌ ‌cycles‌ ‌and‌ ‌cryotransfer.‌ ‌
 
-‌ ‌Carry‌ ‌out‌ ‌an‌ ‌intermediate‌ ‌analysis‌ ‌of‌ ‌the‌ ‌data‌ ‌using‌ ‌"adaptive‌ ‌clinical‌ ‌dessigns".‌ ‌
 
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Third‌ ‌year:‌ ‌
 
-‌ ‌Continuation‌ ‌of‌ ‌IVF/ICSI‌ ‌and‌ ‌cryotransfer‌ ‌cycles.‌ ‌
 
-‌‌Collection‌‌of‌‌data‌‌from‌‌IVF/ICSI‌‌and‌‌neonatal‌‌cycles‌‌and‌‌application‌‌of‌‌statistical‌‌
 
 
 
 
 
 
 
 
 
 
 
 
 
treatment.‌ ‌
 
-‌ ‌Drafting‌ ‌of‌ ‌results‌ ‌
 
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STATISTICAL‌ ‌ANALYSIS‌ ‌PLAN‌ ‌
 
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For‌‌the‌‌purpose‌‌of‌‌testing‌‌the‌‌null‌‌hypothesis‌‌that‌‌shows‌‌equal‌‌live‌‌birth‌‌rates‌‌in‌‌the‌‌
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
group‌‌of‌‌women‌‌who‌‌undergo‌‌elective‌‌deferred‌‌transfer‌‌of‌‌a‌‌single‌‌embryo‌‌and‌‌the‌‌
 
 
 
 
 
 
 
 
   
 
 
 
 
group‌‌that‌‌undergoes‌‌elective‌‌transfer‌‌of‌‌a‌‌fresh‌‌embryo,‌‌a‌‌power‌‌of‌‌80%‌‌has‌‌been‌‌
 
 
 
 
 
   
 
   
 
 
 
 
 
established‌‌to‌‌detect‌‌statistically‌‌significant‌‌differences‌‌using‌‌a‌‌bilateral‌‌Chi-square‌‌
 
 
 
 
 
 
   
 
 
test‌ ‌for‌ ‌two‌ ‌samples,‌ ‌taking‌ ‌into‌ ‌account‌ ‌that‌ ‌the‌ ‌significance‌ ‌level‌ ‌is‌ ‌5%,‌ ‌and‌‌
 
 
 
 
 
 
 
 
 
 
 
 
 
 
assuming‌‌that‌‌the‌‌proportion‌‌in‌‌the‌‌group‌‌of‌‌women‌‌undergoing‌‌a‌‌fresh‌‌transfer‌‌is‌‌
 
 
 
 
 
 
 
 
 
   
 
   
50.9%,‌‌the‌‌proportion‌‌in‌‌the‌‌group‌‌of‌‌women‌‌undergoing‌‌elective‌‌deferred‌‌transfer‌‌is‌‌
 
 
 
 
 
 
 
 
 
 
 
   
78%,‌‌and‌‌that‌‌the‌‌proportion‌‌of‌‌women‌‌out‌‌of‌‌the‌‌total‌‌is‌‌50%,‌‌it‌‌will‌‌be‌‌necessary‌‌to‌‌
 
 
 
 
 
 
 
 
 
 
   
   
 
 
 
 
include‌ ‌48‌ ‌women‌ ‌in‌ ‌each‌ ‌group,‌ ‌for‌ ‌a‌ ‌total‌ ‌of‌ ‌96‌ ‌experimental‌ ‌units‌ ‌in‌ ‌the‌ ‌study.‌ ‌
 
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Taking‌‌into‌‌account‌‌that‌‌the‌‌expected‌‌dropout‌‌rate‌‌is‌‌three‌‌out‌‌of‌‌ten‌‌women,‌‌it‌‌will‌‌
 
 
 
 
 
 
 
   
 
 
 
 
   
 
be‌ ‌necessary‌ ‌to‌ ‌include‌ ‌69‌ ‌women‌ ‌per‌ ‌group.‌ ‌
 
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The‌ ‌assignment‌ ‌of‌ ‌the‌ ‌138‌ ‌women‌ ‌to‌ ‌one‌ ‌of‌ ‌the‌ ‌groups‌ ‌will‌ ‌be‌ ‌carried‌‌out‌‌by‌‌a‌‌
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
randomized‌ ‌procedure,‌ ‌following‌ ‌a‌ ‌sequence‌ ‌of‌ ‌random‌ ‌numbers‌ ‌generated‌ ‌by‌‌
 
 
 
 
 
 
 
 
 
 
specific‌ ‌software‌ ‌(Epidat,‌ ‌Epidemiological‌ ‌Analysis‌ ‌of‌ ‌Tabulated‌ ‌Data‌ ‌Program.‌
 
 
 
 
 
 
 
 
 
Tabulated.‌ ‌Version‌ ‌3.1)‌ ‌
 
‌