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