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Using biomarkers observed by women to inform the probability
of conceptionJoseph B. Stanford, MD, MSPH, CFCMC
Jared Hansen, MStatOffice of Cooperative Reproductive Health
Department of Family and Preventive MedicineUniversity of Utah
2015 July 15
FecundabilityDay-specific probabilities of conceptionFertile window Implantation windowQuestion #1: Impact of coitus in this window on
fecundabilityDifferences in timing of ovulation biomarkersQuestion #2: Impact on fecundability
Mucus scoreQuestion #3: Impact on fecundability
Fecundability
The probability of conception in a menstrual cycle.Depends on cycle viability and coital timing.
Reproductive physiology: ova, sperm, mucus, endometrium, others
Cycle viability Fecundability
Timing of coitus
The consecutive days during a menstrual cycle when coitus has a significant probability of resulting in pregnancy
The fertile window
The fertile window
NFP Chart
1234567891011121314151617181920212223242526272829303132333435
StampRRRRRWBWBWBWBWBPGBGBGBGGGGGGGGGGGG
Date1/281/291/301/312/12/22/32/42/52/62/72/82/82/102/112/122/132/142/152/162/172/182/192/202/21
DescriptionHHLVLVLOADOAD2WX210CX110CX1OAD10CLX1OAD2X32X2OADOADOADOADOADOADOADOADOADOAD
1234567891011121314151617181920212223242526272829303132333435
StampRRRRRRGGGWBWBWBWBWBPGBGBGBGGGGGGGGGGGG
Date2/222/232/242/252/262/272/283/13/23/33/43/53/63/73/83/93/103/113/123/133/143/153/163/173/183/193/203/213/22
DescriptionVLLHLVLVLBOADOAD2X26CX18CKX210KX110KX210CKX1OADOAD2X22X3OADOADOAD2X32X2OADOAD2X3OADOADOAD
1234567891011121314151617181920212223242526272829303132333435
StampRRRRRRRRGGGGGGGGWBWBWBWBWBWBPGBGBGBGGGGGGGGGG
Date3/233/243/253/263/273/283/293/303/314/14/24/34/44/54/64/74/84/94/104/114/124/134/144/154/164/174/184/194/204/214/224/234/244/254/26
DescriptionVLLLMHMLVLOADOADOADOAD2X22X3OADOAD8CKX18KX210CKX110CKX110KX210KX1OADOADOAD2X12X2OADOADOAD2X32X1OADOADOAD
&CNFP Chart
BSE
BSE
BSE
Day-specific probabilities of conception
The probability of pregnancy if coitus occurred only once during the fertile window, on that day
Day-specific probabilities of conceptionPr
obab
ility
of c
once
ptio
n
Day relative to estimated ovulation (day 0)
Implantation window
The days during which an embryo may implant in the endometrium 5-9 days after ovulation/fertilization
Menses Infertile Fertile window Infertile
Ovulation Implantation period
Coitus in the implantation windowSteiner et al. reported that coitus on 2 or more
versus 0 days in the implantation window was associated with lower fecundabilityFecundability ratio 0.62; [95% CI: 0.42–0.91]564 women aged 30 to 44 1,332 cycles (1 to 4 per woman)Adjusted for age, prior pregnancy, race, body-
mass index (BMI)
Steiner AZ et al. Fertil Steril, 2014
Question #1
Does coitus in the implantation window decrease the likelihood of pregnancy? Should couples seeking pregnancy be advised not
to have coitus in the implantation window?
Study population
Data Bank – University of PaduaEuropean Multicenter Fecundability Study 11 sites in EuropeNormal fertility couplesSympto-thermal charting
630 women and 7284 cycles included in analysisMean age 29.5 years (range, 19 to 39 years)
Colombo and Masarotto, Demograph Res, 2000
Cycles by number of days of coitus in implantation window and fecundability
Days of coitus in implantation window
Conceived 0 1 2 or more
No 672 (79%) 690 (81%) 514 (85%)
Yes 175 (21%) 162 (19%) 90 (15%)
Total 847 852 604
p=0.0073
Cycles by days of coitus in implantation and fertile windows
Days of coitus in implantation windowDays of coitus fertile window 0 1 2 or more
0 667 (19%) 1166 (33%) 1713 (48%)
1 261 (34%) 271 (35%) 245 (32%)
2 244 (39%) 251 (41%) 124 (20%)
3 or more 342 (38%) 330 (36%) 235 (26%)p
Accounts for timing of coitus in fertile window to calculate fecundabilityDay-specific probabilities of conception (p)Cycle viability (A)Cycle viability term ( = maximum fecundability)
Pij= A{1 -∏(1- pk)Xjk}i=couple j=cycle k=dayp=day-specific probability x=coitus
Schwartz model
Schwartz D, et al. Population Studies 1980
Day-specific probabilities of conceptionPr
obab
ility
of c
once
ptio
n
Day relative to estimated ovulation (day 0)
Cycle viability by number of days coitus in the implantation window
Number of days with coitus in the implantation window
Cyc
le v
iabi
lity
Why different results?
Steiner et al. had an imprecise way to assess the fertile window (calendar).But they found similar results when using urine LH as
the marker in a subset of cycles.Reverse causationWomen who are already pregnant (even very early)
may be less likely to have intercourse during implantation window.
Conclusions
There is no significant reduction in fecundability from coitus in the implantation window.Couples who wish to conceive do not need to be
advised to avoid coitus in the implantation window.
Question #2
Does a large difference between two biomarkers of ovulation indicate a cycle with lower viability?Day before shift in basal body temperature (BBT)Mucus peak day
Study population
Data Bank – University of PaduaEuropean Multicenter Fecundability Study 11 sites in EuropeNormal fertility couplesSympto-thermal charting
630 women and 7284 cycles included in analysisMean age 29.5 years (range, 19 to 39 years)
Colombo and Masarotto, Demograph Res, 2000
Difference: BBT shift and mucus peak
68 81
150
281
494439
298
172117
0
100
200
300
400
500
600
-4 ormore
-3 -2 -1 0 1 2 3 4 ormore
Num
ber o
f cyc
les
Day before BBT shift minus mucus peak
Cycle viability by difference between BBT shift and mucus peak day (BBT referent)
Number of days between day before BBT shift and mucus peak
Cyc
le v
iabi
lity
Cycle viability by difference between BBT shift and mucus peak day (peak referent)
Cyc
le v
iabi
lity
Number of days between day before BBT shift and mucus peak
Conclusions
There is no significant reduction in fecundability from a larger difference between mucus peak day and BBT shift.
Question #3
How does the probability of pregnancy relate to the Creighton Model mucus score in women using the Creighton Model FertilityCare system?
426 eligible couples309 apparently normal fertility
(trying to avoid pregnancy at entry)1681 eligible cycles81 pregnancies
117 subfertility (trying to achieve pregnancy at entry)373 eligible cycles30 pregnancies
Data from the Creighton Model multicenter fecundability study
Stanford, Smith, Dunson, Obstet Gynecol, 2003
Probability of pregnancy and mucus cycle score
Conclusions
The mucus score relates directly to the probability of pregnancy in couples without a prior history of subfertility.
Related questions
How is the probability of conception impacted byTail end brown bleeding of mensesSplit peaks or multiple peaksPremenstrual spottingGap between mucus peak and urine LH surgeShorter luteal phasesetc.
Office of Cooperative Reproductive Health
Using biomarkers observed by women to inform the probability�of conceptionSlide Number 2FecundabilityThe fertile windowThe fertile windowDay-specific probabilities of conceptionDay-specific probabilities of conceptionImplantation windowCoitus in the implantation windowQuestion #1Study populationCycles by number of days of coitus in implantation window and fecundabilityCycles by days of coitus in implantation and fertile windowsSchwartz modelDay-specific probabilities of conceptionCycle viability by number of days coitus in the implantation windowWhy different results?ConclusionsSlide Number 19Question #2Study populationDifference: BBT shift and mucus peakCycle viability by difference between BBT shift and mucus peak day (BBT referent)Cycle viability by difference between BBT shift and mucus peak day (peak referent)ConclusionsQuestion #3Data from the Creighton Model multicenter fecundability studyProbability of pregnancy and �mucus cycle scoreConclusionsRelated questionsOffice of Cooperative �Reproductive Health