2024
Fibroids and unexplained infertility treatment with epigallocatechin gallate: a natural compound in green tea (FRIEND) – protocol for a randomised placebo-controlled US multicentre clinical trial of EGCG to improve fertility in women with uterine fibroids
Al-Hendy A, Segars J, Taylor H, González F, Siblini H, Zamah M, Alkelani H, Singh B, Flores V, Christman G, Johnson J, Huang H, Zhang H. Fibroids and unexplained infertility treatment with epigallocatechin gallate: a natural compound in green tea (FRIEND) – protocol for a randomised placebo-controlled US multicentre clinical trial of EGCG to improve fertility in women with uterine fibroids. BMJ Open 2024, 14: e078989. PMID: 38216200, PMCID: PMC10806662, DOI: 10.1136/bmjopen-2023-078989.Peer-Reviewed Original ResearchConceptsUnexplained infertilityIntrauterine inseminationInstitutional review boardCumulative live birth rateUterine fibroidsLive birth rateCause of infertilityFood and Drug AdminstrationGonadotropin hormone-releasing hormoneGreen tea extractDouble-blind clinical trialNon-surgical treatment optionsTimed intrauterine inseminationUterine fibroid sizeOvarian stimulationQuality of Life Questionnaire scoresHormone-releasing hormoneLocal institutional review boardInfertility treatmentNational Institute of Child HealthInstitute of Child HealthMiscarriage rateBirth rateReproductive-age womenEndometrial quality
2023
Prednisone vs Placebo and Live Birth in Patients With Recurrent Implantation Failure Undergoing In Vitro Fertilization
Sun Y, Cui L, Lu Y, Tan J, Dong X, Ni T, Yan J, Guan Y, Hao G, Liu J, Zhang B, Wei D, Hong Y, He Y, Qi J, Xu B, Lu J, Zhang Q, Zhao S, Ji X, Du X, Zhang J, Liu J, Wang J, Huang Y, Huang D, Du Y, Vankelecom H, Zhang H, Chen Z. Prednisone vs Placebo and Live Birth in Patients With Recurrent Implantation Failure Undergoing In Vitro Fertilization. JAMA 2023, 329: 1460-1468. PMID: 37129654, PMCID: PMC10155063, DOI: 10.1001/jama.2023.5302.Peer-Reviewed Original ResearchConceptsRecurrent implantation failureFrozen-thawed embryo transferBiochemical pregnancy lossLive birthsImplant failurePlacebo groupPrednisone groupPreterm deliveryEmbryo transferPregnancy lossRisk of preterm deliveryRates of biochemical pregnancyEmbryo transfer cyclesGood-quality embryosLive birth rateLive birth outcomesTreatment of recurrent implantation failureStatistically significant between-group differencesHistory of 2Randomized clinical trialsProbability of implantationImmune-regulatory agentSignificant between-group differencesNeonatal complicationsWeeks gestation
2021
Live Birth with or without Preimplantation Genetic Testing for Aneuploidy
Yan J, Qin Y, Zhao H, Sun Y, Gong F, Li R, Sun X, Ling X, Li H, Hao C, Tan J, Yang J, Zhu Y, Liu F, Chen D, Wei D, Lu J, Ni T, Zhou W, Wu K, Gao Y, Shi Y, Lu Y, Zhang T, Wu W, Ma X, Ma H, Fu J, Zhang J, Meng Q, Zhang H, Legro R, Chen Z. Live Birth with or without Preimplantation Genetic Testing for Aneuploidy. New England Journal Of Medicine 2021, 385: 2047-2058. PMID: 34818479, DOI: 10.1056/nejmoa2103613.Peer-Reviewed Original ResearchConceptsConventional in vitro fertilizationCumulative live birth rateLive birth rateIn vitro fertilizationGood-quality blastocystsPGT-A groupPGT-APreimplantation genetic testingLive birthsGenetic testingClinical pregnancy lossImprove pregnancy outcomesInitial embryo transferEmbryo-transfer proceduresYears of ageNeonatal complicationsPregnancy outcomesSubfertile womenEmbryo transferAdverse eventsPregnancy lossNoninferiority marginEmbryo selectionPrimary outcomeBlastocyst
2020
Factors associated with study protocol adherence and bio banking participation in reproductive medicine clinical trials and their relationship to live birth
Engmann L, Sun F, Legro RS, Diamond MP, Zhang H, Santoro N, Bartlebaugh C, Dodson W, Estes S, Ober J, Brzyski R, Easton C, Hernandez A, Leija M, Pierce D, Robinson R, Awonuga A, Cedo L, Cline A, Collins K, Krawetz S, Puscheck E, Singh M, Yoscovits M, Barnhart K, Coutifaris C, Lecks K, Martino L, Marunich R, Snyder P, Alvero R, Comfort A, Crow M, Schlaff W, Casson P, Hohmann A, Mallette S, Christman G, Ohl D, Ringbloom M, Tang J, Bates G, Mason S, DiMaria N, Usadi R, Lucidi R, Rhea M, Baker V, Turner K, Trussell J, DelBasso D, Huang H, Li Y, Makuch R, Patrizio P, Sakai L, Scahill L, Taylor H, Thomas T, Tsang S, Yan Q, Zhang M, Haisenleder D, Lamar C, DePaolo L, Herring A, Redmond J, Thomas M, Turek P, Wactawski-Wende J, Rebar R, Cato P, Dukic V, Lewis V, Schlegel P, Witter F. Factors associated with study protocol adherence and bio banking participation in reproductive medicine clinical trials and their relationship to live birth. Human Reproduction 2020, 35: 2819-2831. PMID: 33190149, PMCID: PMC8453415, DOI: 10.1093/humrep/deaa232.Peer-Reviewed Original ResearchConceptsPolycystic ovary syndromeClinical trial protocolMedicine clinical trialsU10 HD055942U10 HD38998Baseline characteristicsTrial protocolClinical trialsLive birthsPolycystic Ovary Syndrome IIU10 HD38992U10 HD39005U10 HD27049STUDY FUNDING/COMPETINGMultiple Intrauterine GestationsStudy protocol adherenceUS multicenter trialRegular ovulatory cyclesClinical trial findingsPolycystic ovarian morphologyPARTICIPANTS/MATERIALSROLE OF CHANCELower household incomeAfrican AmericansAspects of adherenceShort-term weight change and live birth among women with unexplained infertility and polycystic ovary syndrome undergoing ovulation induction
Vitek W, Sun F, Hoeger KM, Santoro N, Diamond MP, Zhang H, Legro RS, Network E, Coutifaris C, Christman G, Robinson R, Brzyski R, Schlaff W, Casson P, Trussell J, Eisenberg E, Lamar C, DePaolo L. Short-term weight change and live birth among women with unexplained infertility and polycystic ovary syndrome undergoing ovulation induction. Fertility And Sterility 2020, 114: 1032-1039. PMID: 33036790, PMCID: PMC7953832, DOI: 10.1016/j.fertnstert.2020.06.002.Peer-Reviewed Original ResearchConceptsPolycystic ovary syndromeShort-term weight changeUnexplained infertilityLive birth rateOvulation inductionOvary syndromeWeight changeWeight gainCycles of clomipheneBody mass indexMean weight changeBirth rateRandomized trialsMass indexRegular intercourseIntrauterine inseminationTreatment allocationLive birthsMAIN OUTCOMESecondary analysisWomenWeight assessmentBirthSyndromeInfertilityEndometrial thickness after ovarian stimulation with gonadotropin, clomiphene, or letrozole for unexplained infertility, and association with treatment outcomes
Quaas AM, Gavrizi SZ, Peck JD, Diamond MP, Legro RS, Robinson RD, Casson P, Christman GM, Zhang H, Hansen KR, Network E. Endometrial thickness after ovarian stimulation with gonadotropin, clomiphene, or letrozole for unexplained infertility, and association with treatment outcomes. Fertility And Sterility 2020, 115: 213-220. PMID: 32972733, PMCID: PMC7796980, DOI: 10.1016/j.fertnstert.2020.07.030.Peer-Reviewed Original ResearchConceptsLive birth rateEndometrial thicknessUnexplained infertilityOvarian stimulationRisk ratioLive birthsEMT groupHuman chorionic gonadotropin administrationHigher live birth rateIntrauterine insemination treatmentMean endometrial thicknessMultiple Intrauterine GestationsOvarian stimulation medicationChorionic gonadotropin administrationProspective cohort analysisUnadjusted risk ratioAdjusted risk ratioBirth rateOS-IUIThin endometriumIntrauterine gestationGonadotropin administrationStimulation medicationsClinical trialsTreatment outcomesIntrauterine insemination performance characteristics and post-processing total motile sperm count in relation to live birth for couples with unexplained infertility in a randomised, multicentre clinical trial
Hansen KR, Peck JD, Coward RM, Wild RA, Trussell JC, Krawetz SA, Diamond MP, Legro RS, Coutifaris C, Alvero R, Robinson RD, Casson P, Christman GM, Santoro N, Zhang H. Intrauterine insemination performance characteristics and post-processing total motile sperm count in relation to live birth for couples with unexplained infertility in a randomised, multicentre clinical trial. Human Reproduction 2020, 35: 1296-1305. PMID: 32432326, PMCID: PMC7316499, DOI: 10.1093/humrep/deaa027.Peer-Reviewed Original ResearchConceptsTotal motile sperm countLive birth rateHigher total motile sperm countUnexplained infertilityMulticentre clinical trialMotile sperm countClinical trialsLive birthsOvarian stimulationHCG injectionBirth ratePatient discomfortSperm countTreatment cyclesSecondary analysisEunice Kennedy Shriver National InstituteSTUDY FUNDING/COMPETINGLive birth successMultiple Intrauterine GestationsDuration of infertilityIUI treatment cyclesLive birth outcomesPARTICIPANTS/MATERIALSROLE OF CHANCEYears of ageLive birth after a freeze-only strategy versus fresh embryo transfer in three randomized trials considering progesterone concentration
Yu Y, Zhao S, Li Y, Niu Y, Wei D, Zhang S, Chen ZJ, Zhang H, Legro RS. Live birth after a freeze-only strategy versus fresh embryo transfer in three randomized trials considering progesterone concentration. Reproductive BioMedicine Online 2020, 41: 395-401. PMID: 32600942, DOI: 10.1016/j.rbmo.2020.04.021.Peer-Reviewed Original ResearchConceptsLive birth rateFresh embryo transferProgesterone concentrationsEmbryo transferOvulatory womenRandomized trialsBirth rateHuman chorionic gonadotrophin (HCG) administrationFresh embryo transfer groupCleavage-stage embryo transferFreeze-only strategyHigh ovarian responseInitial embryo transferPolycystic ovary syndromeChorionic gonadotrophin administrationEmbryo transfer groupFrozen embryo transferSingle blastocyst transferBetween-group differencesClinical pregnancyGonadotrophin administrationHCG administrationOvarian responseOvary syndromePrimary outcomePregnancy registry: three-year follow-up of children conceived from letrozole, clomiphene, or gonadotropins
Legro RS, Diamond MP, Coutifaris C, Schlaff WD, Alvero R, Casson P, Christman GM, Rosen RM, Cedars MI, Hansen KR, Robinson R, Baker V, Usadi R, Dodson WC, Estes SJ, Kunselman A, Stetter C, Barnhart KT, Coward RM, Trussell JC, Krawetz SA, Santoro N, Huang H, Zhang H, Eisenberg E, Network R. Pregnancy registry: three-year follow-up of children conceived from letrozole, clomiphene, or gonadotropins. Fertility And Sterility 2020, 113: 1005-1013. PMID: 32386612, PMCID: PMC7376442, DOI: 10.1016/j.fertnstert.2019.12.023.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsChild BehaviorChild DevelopmentChild, PreschoolClomipheneCognitionFemaleFertilityFertility AgentsFollow-Up StudiesGesturesGonadotropinsHumansInfantInfertility, FemaleLetrozoleLive BirthMaleOvulation InductionPolycystic Ovary SyndromePregnancyProspective StudiesRandomized Controlled Trials as TopicRegistriesTreatment OutcomeUnited StatesWeight GainConceptsGN groupMultiple pregnancy rateProspective cohort studyPolycystic ovary syndromeChildren of womenInfertility trialsUnexplained infertilityCohort studyII studyMultiple gestationsOvary syndromeHealth centersInfertility treatmentPregnancy rateInfertility therapyMAIN OUTCOMELTZ groupLetrozoleMacArthur-Bates Communicative Development InventoriesAcademic health centersGonadotropinAbnormal scoresClomipheneCC groupDevelopmental QuestionnaireAndrogenicity and fertility treatment in women with unexplained infertility
Wang ET, Diamond MP, Alvero R, Casson P, Christman GM, Coutifaris C, Hansen KR, Sun F, Legro RS, Robinson RD, Usadi RS, Pisarska MD, Santoro NF, Zhang H, Network I. Androgenicity and fertility treatment in women with unexplained infertility. Fertility And Sterility 2020, 113: 636-641. PMID: 32192596, PMCID: PMC7088440, DOI: 10.1016/j.fertnstert.2019.10.034.Peer-Reviewed Original ResearchConceptsLive birth rateBody mass indexUnexplained infertilityClinical pregnancyMass indexPregnancy lossClinical markersLive birthsAndrogenic activityFree androgen index valuesHigher body mass indexMultivariable logistic regression modelMultiple Intrauterine GestationsNormal uterine cavityHigh waist circumferenceOvarian stimulation treatmentPatent fallopian tubesBirth rateLogistic regression modelsAndrogen markersSerum TTOvarian stimulationRegular mensesInfertility populationIntrauterine gestationThe effect of antioxidants on male factor infertility: the Males, Antioxidants, and Infertility (MOXI) randomized clinical trial
Steiner AZ, Hansen KR, Barnhart KT, Cedars MI, Legro RS, Diamond MP, Krawetz SA, Usadi R, Baker VL, Coward RM, Huang H, Wild R, Masson P, Smith JF, Santoro N, Eisenberg E, Zhang H, Network R. The effect of antioxidants on male factor infertility: the Males, Antioxidants, and Infertility (MOXI) randomized clinical trial. Fertility And Sterility 2020, 113: 552-560.e3. PMID: 32111479, PMCID: PMC7219515, DOI: 10.1016/j.fertnstert.2019.11.008.Peer-Reviewed Original ResearchConceptsMonths of treatmentMale factor infertilityFactor infertilityLive birthsSemen parametersPlacebo groupPrimary outcomeSperm concentrationPlacebo-controlled trialLive birth rateCumulative live birthDNA fragmentationFemale partnersSperm DNA fragmentation indexLycopene dailyVivo pregnancyClomiphene citrateSecondary outcomesEntire cohortAsthenospermic menFertility centerIntrauterine inseminationMonth 4Tubal patencyClinical trials
2019
Optimal timing of antenatal corticosteroid administration and preterm neonatal and early childhood outcomes
Battarbee AN, Ros ST, Esplin MS, Biggio J, Bukowski R, Parry S, Zhang H, Huang H, Andrews W, Saade G, Sadovsky Y, Reddy UM, Varner MW, Manuck TA, Research E. Optimal timing of antenatal corticosteroid administration and preterm neonatal and early childhood outcomes. American Journal Of Obstetrics & Gynecology MFM 2019, 2: 100077. PMID: 32905377, PMCID: PMC7469940, DOI: 10.1016/j.ajogmf.2019.100077.Peer-Reviewed Original ResearchConceptsRespiratory distress syndromeAntenatal corticosteroid administrationEarly childhood morbidityAntenatal corticosteroidsSevere neonatal morbidityChildhood morbidityDistress syndromeNeonatal morbidityCorticosteroid administrationSteroid administrationPreterm neonatesOptimal timingComposite neonatal morbidityPreterm birth researchCourse of corticosteroidsMean gestational ageSpontaneous preterm birthSpontaneous preterm laborProspective multicenter studyLong-term outcomesMultivariable logistic regressionEarly childhood outcomesAntenatal magnesiumNeonatal outcomesPreterm laborCervicovaginal fluid proteomic analysis to identify potential biomarkers for preterm birth
Parry S, Leite R, Esplin MS, Bukowski R, Zhang H, Varner M, Andrews WW, Saade GR, Ilekis J, Reddy UM, Huang H, Sadovsky Y, Blair IA, Biggio J, Research E. Cervicovaginal fluid proteomic analysis to identify potential biomarkers for preterm birth. American Journal Of Obstetrics And Gynecology 2019, 222: 493.e1-493.e13. PMID: 31758918, PMCID: PMC7196033, DOI: 10.1016/j.ajog.2019.11.1252.Peer-Reviewed Original ResearchConceptsPreterm birth casesSpontaneous preterm birthCervicovaginal fluid samplesEnzyme-linked immunosorbentTerm delivery controlsPreterm birthStudy visitBirth casesFluid samplesPotential biomarkersSpontaneous preterm birth ratePrior spontaneous preterm birthEarly spontaneous preterm birthCervical length screeningThird study visitVaginal mucosal cellsPreterm birth rateHigh-risk cohortCase-control studyReliable screening testAvailable biological fluidIndependent study groupsNeonatal morbidityObstetrical historyAsymptomatic womenFirst-line ovulation induction for polycystic ovary syndrome: an individual participant data meta-analysis
Wang R, Li W, Bordewijk E, Legro R, Zhang H, Wu X, Gao J, Morin-Papunen L, Homburg R, König T, Moll E, Kar S, Huang W, Johnson N, Amer S, Vegetti W, Palomba S, Falbo A, Özmen Ü, Nazik H, Williams C, Federica G, Lord J, Sahin Y, Bhattacharya S, Norman R, van Wely M, Mol B, Network+ R, Collaboration T. First-line ovulation induction for polycystic ovary syndrome: an individual participant data meta-analysis. Human Reproduction Update 2019, 25: 717-732. PMID: 31647106, DOI: 10.1093/humupd/dmz029.Peer-Reviewed Original ResearchConceptsPolycystic ovary syndromeClinical pregnancy rateClomiphene citrateLive birth rateOvulation inductionTime-to-pregnancyAnovulatory infertilityFrequent cause of anovulatory infertilityPregnancy rateCause of anovulatory infertilityBirth rateMetformin to CCOvulation induction agentsIncreased clinical pregnancyLive birthsPrimary randomised controlled trialsClinical pregnancyRandomised controlled trialsInfertilityIndividual participant dataIPD meta-analysesWomenPositive interactionsLetrozoleAccurate assessment of outcomesFresh versus frozen blastocyst transfer – Authors' reply
Wei D, Zhang H, Legro RS, Chen ZJ. Fresh versus frozen blastocyst transfer – Authors' reply. The Lancet 2019, 394: 1228. PMID: 31303315, DOI: 10.1016/s0140-6736(19)31390-x.Peer-Reviewed Original ResearchAssociation between testosterone, semen parameters, and live birth in men with unexplained infertility in an intrauterine insemination population
Trussell JC, Coward RM, Santoro N, Stetter C, Kunselman A, Diamond MP, Hansen KR, Krawetz SA, Legro RS, Heisenleder D, Smith J, Steiner A, Wild R, Casson P, Coutifaris C, Alvero RR, Robinson RB, Christman G, Patrizio P, Zhang H, Lindgren MC, Network R. Association between testosterone, semen parameters, and live birth in men with unexplained infertility in an intrauterine insemination population. Fertility And Sterility 2019, 111: 1129-1134. PMID: 30982604, PMCID: PMC6557574, DOI: 10.1016/j.fertnstert.2019.01.034.Peer-Reviewed Original ResearchMeSH KeywordsAdultBiomarkersDown-RegulationFemaleFertilityHumansInfertility, MaleInsemination, Artificial, HomologousLive BirthMaleMulticenter Studies as TopicPregnancyPregnancy RateRandomized Controlled Trials as TopicRisk FactorsSperm CountSperm MotilitySpermatogenesisTestosteroneTreatment OutcomeConceptsUnexplained infertilityLow TTMale partnersLive birthsSemen parametersSecondary analysisMultiple Intrauterine GestationsLive birth rateBody mass indexMulticenter clinical trialAbnormal sperm morphologyOvarian stimulationIntrauterine gestationPregnancy outcomesMass indexInfertility clinicClinical trialsMAIN OUTCOMETotal motile spermSemen analysisAbnormal spermatogenesisInfertilityLogistic regressionSperm concentrationSemen volumeFrozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial
Wei D, Liu J, Sun Y, Shi Y, Zhang B, Liu J, Tan J, Liang X, Cao Y, Wang Z, Qin Y, Zhao H, Zhou Y, Ren H, Hao G, Ling X, Zhao J, Zhang Y, Qi X, Zhang L, Deng X, Chen X, Zhu Y, Wang X, Tian L, Lv Q, Ma X, Zhang H, Legro R, Chen Z. Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial. The Lancet 2019, 393: 1310-1318. PMID: 30827784, DOI: 10.1016/s0140-6736(18)32843-5.Peer-Reviewed Original ResearchConceptsFrozen single blastocyst transferFresh single blastocyst transferSingle blastocyst transferElective single embryo transferRisk of pre-eclampsiaFrozen blastocyst transferBlastocyst transferLivebirth rateSevere ovarian hyperstimulation syndromePre-eclampsiaOvulatory womenPregnancy rateEmbryo transferOvarian hyperstimulation syndromeAcademic fertility centreFrozen-thawed single blastocyst transferHigher risk of pre-eclampsiaIn vitro fertilisationIncreased risk of pre-eclampsiaFrozen embryo transferExtended embryo cultureSingle embryo transferFertility centreHyperstimulation syndromeLower pregnancy rate
2018
Optimal treatment for women with a persisting pregnancy of unknown location, a randomized controlled trial: The ACT-or-NOT trial
Barnhart KT, Sammel MD, Stephenson M, Robins J, Hansen KR, Youssef WA, Santoro N, Eisenberg E, Zhang H, Network F. Optimal treatment for women with a persisting pregnancy of unknown location, a randomized controlled trial: The ACT-or-NOT trial. Contemporary Clinical Trials 2018, 73: 145-151. PMID: 30243810, PMCID: PMC6231403, DOI: 10.1016/j.cct.2018.09.009.Peer-Reviewed Original ResearchConceptsOutcome measuresHuman chorionic gonadotropin concentrationRuptured ectopic pregnancyPositive pregnancy testSecondary outcome measuresExtra-uterine pregnancyInitial management strategyPrimary outcome measureChorionic gonadotropin concentrationsPatient satisfaction outcomesInitial management planAcademic medical centerEvidence-based managementAdditional ultrasonographyPersistent PULEctopic pregnancyExpectant managementAdverse eventsClinical resolutionEmpiric useGonadotropin concentrationsTransvaginal ultrasonographyTreatment complicationsTreatment armsUterine evacuationComparison of sonohysterography to hysterosalpingogram for tubal patency assessment in a multicenter fertility treatment trial among women with polycystic ovary syndrome
Christianson MS, Legro RS, Jin S, Eisenberg E, Diamond MP, Hansen KR, Vitek W, Styer AK, Casson P, Coutifaris C, Christman GM, Alvero R, Puscheck EE, Christy AY, Sun F, Zhang H, Polotsky AJ, Santoro N. Comparison of sonohysterography to hysterosalpingogram for tubal patency assessment in a multicenter fertility treatment trial among women with polycystic ovary syndrome. Journal Of Assisted Reproduction And Genetics 2018, 35: 2173-2180. PMID: 30194618, PMCID: PMC6289919, DOI: 10.1007/s10815-018-1306-2.Peer-Reviewed Original ResearchConceptsPolycystic ovary syndromeSaline infusion sonohysterographyTubal patencyClinical pregnancyOvary syndromePolycystic Ovary Syndrome IITubal patency assessmentClinical pregnancy rateDuration of infertilityAcceptable imaging modalityIntrauterine pregnancyClomiphene citrateEctopic pregnancyInfertile womenResultsAmong womenMultivariable analysisPatency assessmentTreatment armsTreatment trialsPregnancy rateMethodsSecondary analysisHysterosalpingogramLarge cohortTubes patentPatencyVitamin D Deficiency Is Associated With Poor Ovarian Stimulation Outcome in PCOS but Not Unexplained Infertility
Butts SF, Seifer DB, Koelper N, Senapati S, Sammel MD, Hoofnagle AN, Kelly A, Krawetz SA, Santoro N, Zhang H, Diamond MP, Legro RS, Network E. Vitamin D Deficiency Is Associated With Poor Ovarian Stimulation Outcome in PCOS but Not Unexplained Infertility. The Journal Of Clinical Endocrinology & Metabolism 2018, 104: 369-378. PMID: 30085176, PMCID: PMC6300410, DOI: 10.1210/jc.2018-00750.Peer-Reviewed Original ResearchConceptsVitamin D deficiencyPolycystic ovary syndromeD deficiencyEarly pregnancy lossOvarian stimulationUnexplained infertilityLive birthsPregnancy lossDiagnosis of PCOSMultiple Intrauterine GestationsOvarian stimulation outcomesRetrospective cohort studyInvestigation of womenBanked seraPPCOS IICohort studyIntrauterine gestationOvary syndromeInfertile womenInfertility diagnosisPregnant subjectsElevated riskImportant treatmentReproductive outcomesTrial data