Is Maternal Is Maternal Menstrual Cycle Menstrual Cycle

Length Associated Length Associated with Twinning?with Twinning?

Author 1Author 1

Author 2Author 2

BackgroundBackground Menstrual Cycles & TwinningMenstrual Cycles & Twinning

– Shorter cycles -- Shorter cycles -- ↑↑ T Twinning winning Time to Pregnancy (TTP) & TwinningTime to Pregnancy (TTP) & Twinning

– ↓↓ TTP -- TTP -- ↑↑ T Twinning winning Menstrual Cycles & FertilityMenstrual Cycles & Fertility

– Regular menstrual cycles -- Regular menstrual cycles -- ↑↑ Fertility Fertility

– Short & long cycles -- Short & long cycles -- ↑ ↑ Spontaneous Spontaneous abortionabortion

Body Mass IndexBody Mass Index– ↑↑ BMI -- long, irregular cyclesBMI -- long, irregular cycles

– ↑↑ BMI -- BMI -- ↑↑ twinning twinning

Why this question?Why this question? Goal to determine whether menstrual cycle Goal to determine whether menstrual cycle

characteristics can act as a surrogate for characteristics can act as a surrogate for reproductive healthreproductive health

““Natural” twinning trends may be used as an Natural” twinning trends may be used as an indicator of reproductive healthindicator of reproductive health

Unique cohort to study twinningUnique cohort to study twinning– 223 Twins223 Twins– Before ART and OC use were commonBefore ART and OC use were common

Menstrual cycle length was asked before Menstrual cycle length was asked before birth outcome (less recall bias)birth outcome (less recall bias)

Study PopulationStudy Population

Initial Dataset N= 20530

Missing Menstrual Cycle Length (N= 8847)

Menstrual Cycles N=11683

Oral contraception (N=668)

No Oral Contraception N=11015

Medications for thyroid, fertility, or any other hormonal medication (N=1584)

No Other Hormonal Medications Final Dataset

N= 9431 Same sex twins (N=66)

Discordant Sex Twins Dataset N= 9465

97 Twins97 Twins

31 Twins31 Twins

Exposure & OutcomeExposure & Outcome Menstrual Cycle Length:Menstrual Cycle Length:

– Short (<25 days)Short (<25 days)– Average (25-35 days)Average (25-35 days)– Long/Irregular (> 35 days)Long/Irregular (> 35 days)

Twinning:Twinning:– In CHDS: 223/20307 births (1.07%)In CHDS: 223/20307 births (1.07%)– Final dataset - 97 twinsFinal dataset - 97 twins– Discordant sex twin dataset - 31 twinsDiscordant sex twin dataset - 31 twins

Univariate AnalysesUnivariate Analyses

Age*Age* Race* Race* Education*Education* Pre-pregnancy BMIPre-pregnancy BMI Current BMICurrent BMI Smoking status*Smoking status* Cigarettes/day*Cigarettes/day*

Alcohol useAlcohol use Coffee intake*Coffee intake* Tea intakeTea intake Age of menarche*Age of menarche* Pregnancy Pregnancy

outcomeoutcome ParityParity Interval between Interval between

pregnanciespregnancies * Associated with menstrual cycle length

Associated with twinning

Chi Square AnalysesChi Square AnalysesNumber and percents of singletons and twins for each category of menstrual cycle length, Child Health and Development Studies, Oakland, CA, 1959-1967.

Menstrual Cycle Length

Outcome

Shortn=597 (6.3%)

Averagen=6639 (69.7%)

Long/ Irregular

n=777 (24.0%)

P- value

Singletons 575 (98.1) 6492 (98.9) 2267 (99.4)

9.3

0.01

Twins 11 (1.9) 73 (1.1) 13 (0.6)

Bivariate AnalysesBivariate AnalysesProportion of Twinning (%)

CharacteristicCharacteristic

Short Cycle

n=586

AverageCycle

n=6565

Stratum-Specific

RR (95% CI)

Mantel-Haenszel

RR (95% CI)

Breslow-Day

Test for Homo-geneity

All 1.9 1.1 NA 1.7 (0.9, 3.2) NA

Education NA 3.2 (0.1)

<= High School 0.7 1.0

> High School 3.2 1.2

Log likelihood test: Wald =3.88 p=0.14

Bivariate AnalysisBivariate AnalysisProportion of Twinning (%)

CharacteristicCharacteristic

Long/Irreg

n=2280

AverageCycle

n=6565

Stratum-Specific

RR (95% CI)

Mantel-Haenszel

RR (95% CI)

Breslow-Day

Test for Homo-geneity

All 0.6 1.1 NA 0.5 (0.3, 0.9) NA

Age NA 9.7 (0.1)

<20 0.80.8 0.00.0 NANA

20-24 0.30.3 1.11.1 0.2 (0.1, 1.1)0.2 (0.1, 1.1)

25-29 0.40.4 1.21.2 0.3 (0.1, 1.1)0.3 (0.1, 1.1)

30-34 0.80.8 1.41.4 0.6 (0.1, 2.5)0.6 (0.1, 2.5)

>34 0.80.8 1.41.4 0.6 (0.1, 2.5)0.6 (0.1, 2.5)

Log likelihood test: Wald =12.0 p=0.21

Multivariable AnalysesMultivariable Analyses

Crude ModelCrude Model Odds RatioOdds Ratio 95% CI95% CI

ShortShort 1.701.70 (0.90, 3.23)(0.90, 3.23)

Long/ IrregularLong/ Irregular 0.510.51 ((0.28, 0.920.28, 0.92))

Multivariable AnalysesMultivariable Analyses

Crude ModelCrude Model Odds RatioOdds Ratio 95% CI95% CI

ShortShort 1.701.70 (0.90, 3.23)(0.90, 3.23)

Long/ IrregularLong/ Irregular 0.510.51 ((0.28, 0.920.28, 0.92))

Adjusted ModelAdjusted Model

Short Short 1.831.83 (0.96, 3.51)(0.96, 3.51)

Long/ IrregularLong/ Irregular 0.530.53 ((0.29, 0.980.29, 0.98))

AgeAge 1.011.01 (0.98, 1.05)(0.98, 1.05)

Pre-pregnancy BMIPre-pregnancy BMI 1.101.10 (0.64, 1.90)(0.64, 1.90)

Race Race 1.411.41 (0.92, 2.16)(0.92, 2.16)

Parity Parity 1.991.99 (1.09, 3.63)(1.09, 3.63)

SmokeSmoke 1.521.52 (0.99, 2.33)(0.99, 2.33)

Age of menarcheAge of menarche 1.361.36 (0.83, 2.22)(0.83, 2.22)

Multivariable AnalysesMultivariable Analyses

Crude ModelCrude Model Odds RatioOdds Ratio 95% CI95% CI

ShortShort 1.701.70 (0.90, 3.23)(0.90, 3.23)

Long/ IrregularLong/ Irregular 0.510.51 ((0.28, 0.920.28, 0.92))

Restricted to Different Sex TwinsRestricted to Different Sex Twins

ShortShort 3.083.08 ((1.24, 7.631.24, 7.63))

Long/ IrregularLong/ Irregular 0.390.39 (0.12, 1.31)(0.12, 1.31)

ConclusionConclusion

Found association between menstrual Found association between menstrual cycle length and twinningcycle length and twinning

Limitations include the large amount of Limitations include the large amount of missing datamissing data

Potential confounders did not change the Potential confounders did not change the estimate of the effectestimate of the effect

Interaction was not significantInteraction was not significant

Future DirectionsFuture Directions

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DZ DZ MZ MZ

Restricted Data Set

Potential Exclusions