Effect of IVF failure on quality of life and emotional status in infertile couples

Effect

of

IVF

failure

on

quality

of

life

and

emotional

status

in

infertile

couples

Nilay

Karaca

*

,

Aysun

Karabulut

,

Sevgi

Ozkan

,

Hale

Aktun

,

Fatma

Orengul

,

Rabiye

Yilmaz

,

Seda

Ates

,

Gonca

Batmaz

a_{BezmialemVakifUniversity,SchoolofMedicine,DepartmentofObstetricandGynecology,Istanbul,Turkey} b

PamukkaleUniversity,SchoolofMedicine,DepartmentofObstetricandGynecology,Denizli,Turkey

c

PamukkaleUniversity,DenizliHealthServicesVocationalCollege,Denizli,Turkey

d

MedipolUniversity,SchoolofMedicine,DepartmentofObstetricandGynecology,Istanbul,Turkey

e

HasekiTrainingResearchHospital,Istanbul,Turkey

ARTICLE INFO Articlehistory: Received16March2016

Receivedinrevisedform9September2016 Accepted13September2016

Keywords: FertiQoL Anxiety Depression

UnsuccesfulIVFtreatment

ABSTRACT

Objective:ToinvestigatetheeffectofapreviousIVFfailureonthequalityoflifeandemotionaldistress,in couplesundergoingIVFtreatment.ExperiencingIVFfailuremightcausedifferencesonthe anxiety-depressionandqualityoflifescoresofthecouples,comparedtotheoneswhowereundergoingIVF treatmentforthefirsttime.

Studydesign:Thisstudyincluded64coupleswhohadpreviouslyexperiencedatleastoneIVFfailure (Group1)and56coupleswithouthistoryofIVFfailure(Group2)inaprivateAssistedReproductive Center,Istanbul,Turkey.Asociodemographicdataform,theFertiQoLInternationalandHospitalAnxiety (HAD-A)andDepressionscale(HAD-D)forevaluatingthestatusofdistress,wereadministeredforthe study.

Result(s):FertiQoLscoreswerecomparedbetweenthegroups,theenvironmentscaleofthequalityoflife intreatmentsectionwasfoundtobesignificantlyhigherinGroup1comparedwithGroup2(p=0.009). TheHAD-AandHAD-Dscoresdidnotdiffersignificantlybetweenthegroups.Group-variableswere investigatedusingmultilevelanalysis,theinfertilitydurationandincomelevelwerefoundtohavean effectonthesubscalesofqualityoflife(p=0.009andp=0.001respectively)inGroup2.Depression scores werehigherin couples withinfertilityduration ofbelowfiveyears in Group1 and Group 2comparedtocoupleswithinfertilitydurationoffiveyearsorabove(MANOVAanalysis).Thelevelof educationwasfoundtoaffectthescoresofHAD-DinGroup2,butnotinGroup1(p=0.011).Thescoreof HAD-DwassignificantlyaffectedbythefamilytypeonlyinGroup2(p=0.009);thedepressionscoreof thecoupleslivingwithanuclearfamilywasfoundtobehighercomparedwiththecoupleslivingina traditionalfamily(p=0.021).

Conclusion(s):Fertility-specificqualityoflifescoresrevealsbetterresultsregardingtheorientationtothe treatmentenvironmentinthecoupleswithapreviousIVFfailure,comparedtofirstIVFcyclecouples. Treatmentfailuredoesnotelevatethelevelofanxiety,whiletheeffectondepressionscoreschanges accordingtodurationofinfertility.

ã2016ElsevierIrelandLtd.Allrightsreserved.

Introduction

Infertilityisdefinedasfailuretoachieveclinicalpregnancyafter twelvemonthsofregularunprotectedsexualintercourse[1].Itis animportantproblemthataffectsaboutonein10couples[2–5].It

mayaffecttherelationshipofcoupleswiththeirfamilies,friends, and each other, and may decrease their self-confidence with feelingsofguiltandinsufficiency[6–8].

Furthermore,proceduresusedindiagnosisandtreatmentmay affectthe couplesand regrettably leadtoemotional stressand decreaseinqualityoflife[9,10].

In the literature, psychosocial studies revealed a higher frequency of negativeattitudes in infertileindividuals, such as dissatisfaction, unwillingness and disorientation regarding the treatment[5,11].Thereforeitisextremelyimportanttoevaluate

*Corresponding author at: Merkez Efendi Mah. Mevlana Cad. Topkapı MerkezevleriA1-41,Zeytinburnu,Istanbul34200,Turkey.Tel.:+9050577253 07;fax:+902124532943.

E-mailaddress:karacanilay@hotmail.com(N.Karaca).

http://dx.doi.org/10.1016/j.ejogrb.2016.09.017

0301-2115/ã2016ElsevierIrelandLtd.Allrightsreserved.

ContentslistsavailableatScienceDirect

European

Journal

of

Obstetrics

&

Gynecology

and

Reproductive

Biology

the couples with their psychosocialbackground and minimize distracting factors in order to maintain the orientation of the patientstothetreatment.

WorldHealth Organization defines the qualityof life as‘an individual’sperceptionoftheirpositioninlifeinthecontextofthe culture,religionand valuesystemsinwhich theylive’,andthis concepthasgraduallygainedimmenseimportanceincomplexand multidirectional health conditions, like infertility [2,12–14]. FollowingthestudybyMenningetal.inthe1980sreportingthat infertilecouplesrequiredpsychologicalsupport,manyresearchers haveinvestigatedthequalityoflifeandpsychologicalstatusofthe infertilecouples,predominantly bynonspeci_fictools evaluating general health status (e.g., WHO-BREF) [15–17]. Later on, the studies reporting the negative social and mental effects of infertilityoncoupleshavegainedgreatimportance,andalimited number of studies have been conducted using more specified formsthatevaluatequalityoflife[2,6,10,16,18]likeFertilityQuality of Life Questionnaire which is an international and condition-specifictoolthatevaluatestheeffectsofinfertilityonqualityoflife in a more realistic way, and reveals more objectively the psychometriccharacteristicsofindividuals[6,11,19].

Themethodofinvitrofertilization,whichisoneofthemost important and final steps in the treatment of infertility, is a therapeuticcoursethatleadstoanxietyincouplesespeciallyin females, and has stressful consequences both socially and financially[4,11,20,21].Twoimportant studieshaveshown that therateofdepressivesymptomsininfertilewomenissignificantly higher, compared with fertile women [22,23]. In addition unsuccessful treatment raised the women’s levels of negative emotions,whichcontinuedafterconsecutiveunsuccessfulcycles. Ingeneral,mostwomenprovedtoadjustwelltounsuccessfulIVF, although a considerable group showed subclinical emotional problems[10].

In the light of the present literature, we hypothesized that experiencingIVFfailuremightcausedifferencesonthe anxiety-depressionandqualityoflifescoresofthecouples,comparedto theoneswhowereundergoingIVFtreatmentforthefirsttime.The objectiveofthepresentstudywastoinvestigatetheeffectofa previousIVFfailureonthequalityoflifeandemotionalstatus,in couplesundergoingIVFtreatment.

Materialsandmethods

Thisdescriptivestudywasconductedusingacross-sectional, pilotstudydesignbetweenApril2014andNovember2014.Ethical approvalwas obtainedfrom theinstitutional Ethics Committee (Internal Review Boards-IRB) at Pamukkale University Medical School(Denizli,Turkey)priortothecollectionofdata.Theresearch teamadheredtotheethicalstandardssetfortheDeclarationof HelsinkiandtheIRBGuidelinesofPamukkaleUniversityMedical School.Writteninformedconsentwasobtainedfromeachpatient toparticipateintothestudy.

Studypopulation

Study population was recruited from patients who were meetingthedefinitionofinfertilityacceptedbytheWHOcriteria

[24] andundergoing invitro fertilizationin a privateinfertility clinic, _Istanbul,Turkey.

Informed consent was obtained from 64 couples who previously experienced at least one in vitro fertilization cycle (IVF)failure(128subjects—Group1),and56coupleswhowouldbe undergoingIVF procedure and having no history of IVF-failure previously(112subjects—Group2).However,fourcoupleswithIVF failure (eight subjects) and nine couples without IVF failure (18 subjects) were subsequently disqualified and eliminated

afterone or both members of those pairs failedto respond to allitemsinthestudyquestionnaire.Instudy’sparticipantpool, the period of infertility ranged from one totwenty-five years withameanageoftwenty-sevenyearsforthefemalesand forty-four years for the males. The socioeconomic status extended across low, middle, and high income earning levels with a majorityofcouplesowninghealthinsuranceduetothenational healthinsuranceprogram.

Datacollectionandquestionnaires

Allthe formswerepresentedtothecouples individually in facetofacefashionbyatrainednurseaboutboththesubjectand the IVF treatment. Aims of the study and content of the questionnaire were explainedtoall participants andinformed consentwasobtainedpriortoimplementinganydatacollection protocols. The couples were separated from their partners to preventmutualeffect,andtheycompletedthequestionnairesina different room from their mate. At both rooms, a nurse was availabletoprovideexplanatorysupportduringthefillingperiod ofthequestionaires.

Thecharacteristicsknowntobeimportantfromourprevious studyandpersonalexperiences wereusedtoobtaindataabout demographic characteristics in themodel [11].A questionnaire composed of 20 structured questions requesting information aboutthechronologicalage,levelofeducation,professionalstatus, socialsecurity,incomelevel,livingplace,typeoffamily,ageatthe time of marriage, cause and duration of infertility, previous methodsoftreatment,previoushistoryofpregnancyanddesirefor psychological support together with theFertiQoL International, whichisthescaleofqualityoflifeforindividualswhoexperience problems of infertility, and Hospital Anxiety (HAD-A) and Depression (HAD-B) scale for evaluating the status of distress, were administered to the attendees. FertiQoL and anxiety-depressionscoresofthecouplesweredefinedasthedependent variablesofthestudy,whereasallotherparametersformedthe independentvariables.

FeriQoL

The infertilecouples’qualityof lifewas measured usingthe FertiQoL scale, which has been translated into 20 languages, includingTurkish. Thevalidityand reliabilityof this likert-type scale was performed by Boivin et al. in 2011 [2]. A Turkish translationoftheFertiQoLquestionnairewasusedinthisstudy

[19].TheTurkishversionofthetoolwasvalidatedaccordingtothe FertiQoLgroupguidelinesfortransculturalresearch[19].

It is a more sensitive, reliable and validmeasure of QoL in infertilitycomparedtogeneralmeasuresofQoLsuchasthe WHO-BREFandSF-36[6].Itwasusedtoassesstheinfluenceoffertility problemsindiverseareassuchasself-esteem,emotions,general health, familyand social relationships,worklifeand future life plans[19].

The FertiQoL questionnaire consists of two parts; Core and Treatment sections. Core FertiQoL items consist of 24 specific questionscoveringfoursubscalesofQoL:Mind&Body,Relational, Social and Emotionaldomains. Theoptional secondpartof the FertiQoLwastheTreatmentmodule,consistingof10questionsand Environment and Tolerability domains. The FertiQoL is a likert scale,andyieldssixsubscaleswitharangeof0–100.Ahigherscore on any subscale means a betterQoL [2]. Twoadditional items (markedAandB)ontheFertiQoLquestionnairecaptureanoverall evaluationofphysicalhealthandsatisfactionwithqualityoflife. Theseareusedforbackgroundinformationbutarenotusedinthe FertiQoLtotalorsubscalescores.

HospitalAnxietyandDepressionscale

HAD scale was used for the measurement of anxiety and depression.Turkishvalidationofthescalewasperformedinby Aydemiretal.in1997[25].Thisscalewasadministeredtoscreen mood disorders in the couples; it evaluates the subjective degradationof moodratherthanphysicalsigns.Thedepression subscale evaluates anhedonia as a main symptom instead of sadness;anhedonicsymptomsareeffectiveproofofdepressionin cases with disease states like infertility, which do not involve suicidalthoughts,a feeling ofguilt and despair.TheHAD scale consistsofatotalof14questionsmainlyregardingthedepression (sevenquestions)andanxiety(sevenquestions),anditisscored between0and21points.Thescoresfrom0to7interpretedas normal,8to10asmild,11to14asmoderateand15to21assevere mooddisorder[25].

Dataanalysis

Statistical analysis was performedusing SPSS10.0 software (SPSSInc.(2000)SPSSforWindows,version10.0.Chicago,IL:SPSS Inc.). Continuous variables were expressed as meanstandard deviationandcategoricalvariablesasnumbersandpercentages. The sociodemographicvariables and other characteristics were analyzedusingdescriptivestatistics,andcomparisonsof means and proportions were conducted with the Chi-square test. Multilevelmultivariateanalysis(MANOVA)wasusedtoevaluate the differences in FertiQoL and HAD scores and independent variables. The independent variables wereage, education, em-ployment status, health insurance, family type, income level, durationofinfertility,causeofinfertility(male,female,both,and unexplained),andthedesireforpsychologicalsupport.Apvalueof lessthan0.05wasconsideredtobestatisticallysignificant. Results

Atotal of107infertilecoupleswereincludedintothestudy. SixtycoupleswithatleastoneIVFfailurepreviouslywereanalyzed inGroup1,and47coupleswhohadnoIVFfailurehistoryformed the Group 2. Demographic and fertility characteristics of the groups(Group1;n=120,Group2;n=94)areshowninTable1.The socioeconomicstatus andeducational level wereslightlylower inGroup 1,and the nuclearfamily type was more commonin Group2.

TheCoreFertiQoLscoresweregenerallyhigherinGroup2than thoseinGroup1;butthisdifferencecouldnotachievestatistical significance(p>0.05).Thetotal,treatmentandtolerabilityscores of FertiQoL, and HAD-A and HAD-D scores did not differ significantly between the two groups (p>0.05) but, in the treatmentsection environment domainscoresof thequalityof lifeinGroup1werefoundtobesigni_ficantlyhighercomparedwith Group2(p=0.009)(Table2).

Multilevel multivariate analysis was used to evaluate the demographic variables based on FertiQoL and HAD scores accordingtoIVF failurehistory (Table3).Durationof infertility andincomelevelwasfoundtohaveaneffectonthesubscalesof qualityoflife,comparedwithothersociodemographicvariables (p=0.009 and p=0.001 respectively) in Group 2. We detected higherscoresinenvironmentsubscaleoftheFertiQoLincouples withdurationofinfertility lessthanfiveyearscomparedtothe ones with 5 years or above (meanSD; 53.362.75 vs. 39.483.42) (F=8.786,p=0.003).Similarly, tolerabilitydomain score was also detected higher in cases with the duration of infertilitybelowfiveyearsinGroup2,comparedtocoupleswithan infertilitydurationoffiveyearsorabove(meanSD54.443.46 vs.43.553.85)(F=4.112p=0.044)(Table3).

WhentheenvironmentsubscaleofFertiQoLwasinvestigated togetherwiththeincomelevelinGroup2,thescoreofthecouples withlowincomewasfoundlowercomparedtothecoupleswith middle and high income (mean_SD; 10.86_3.12 vs. 52.612.82and42.473.90respectively)(F=9.229,p<0.0001). Similarly,theevaluationoftolerabilitysubscaletogetherwiththe incomelevel, showedlowerscoresincoupleswithlowincome comparedtothecoupleswithmiddleandhighincomeinGroup2 (meanSD; 18.752.33 vs. 55.083.21 and 42.544.4) (F=5.237,p=0.006).Thesubscalesofqualityoflifedidnotdiffer significantly regarding theother variables betweenthe groups (p>0.05)(Table3).

TheresultsofMANOVAanalysisoftheHADscoresrevealedno significant differences between the groups and the variables excepttheinfertilityduration,levelofeducationandthefamily type (p>0.05). Depression scores in couples with infertility durationof belowfiveyears werehighercompared totheones with infertility duration of five years or above in Group 1 (meanSD; 10.402.89 vs. 9.492.45), whereas lower

Table1

Demographiccharacteristicsofthestudypopulation. Variables Group1 (n=120) Group2 (n=94) p Value Mean(SD) orn(%) Mean(SD) orn(%) Age 30years 25(20.9) 18(19.1) 0.26 31–35years 53(44.2) 33(35.1) >35years 42(35.0) 43(45.7) Educationalstatus <5years 35(29.4) 24(25.5) 0.037* 6–11years 54(45.4) 31(33.3) >11years 30(25.2) 39(41.5) Incomelevela ClassA 16(13.3) 4(4.3) 0.027* ClassB 78(65.0) 59(62.8) ClassC 26(21.7) 31(33.3) Durationofinfertility <5years 65(54.2) 52(55.3) 0.87 5years 55(45.8) 42(44.7) Healthinsurance Present 117(97.5) 93(98.9) 0.44 Absent 3(2.5) 1(1.1) Causesofinfertility Female 33(28.0) 32(34.4) 0.83 Male 25(21.2) 18(19.4) Both 22(18.6) 13(14.0) Unexplained 38(32.2) 30(32.2) Employmentstatus Employed 81(67.5) 58(61.7) 0.38 Unemployed 39(32.5) 36(38.3) Familytype Nuclearfamily 106(88.3) 92(97.9) 0.008* Extendedfamily 14(11.7) 2(2.1) Requirementforpsychological

support

Yes 15(12.6) 17(18.1) 0.27 No 105(87.4) 77(81.9)

GroupI;coupleswithhistoryofIVFfailure;GroupII;coupleswithouthistoryofIVF failure.

a _{Incomelevel;ClassAhigh;moreincomecomparedtoexpenses,ClassBmiddle;}

incomeandexpenselevelsalmostequal,ClassClowincome,expensesusuallymore thanincome.

*

depressionscoresweredetectedinthecoupleswithdurationof infertilitylessthan5yearscomparedtotheoneswithfiveyearsor above in Group 2 (meanSD; 9.802.64 vs. 11.592.58) (F=13.347p<0.000)(Table4).

InanalysisofHAD-AandHAD-Dscoreswiththegroupandlevel of education; HAD-D scores detected higher in cases with educationallevelbelowhigh-schoolcompared totheuniversity

graduates in Group 2 (meanSD; 11.272.59 vs. 9.662.72) (F=7.020,p=0.009).ScoresofHAD-Adidnotdiffersignificantly betweenthegroupsrelatedtoeducationallevels(p>0.05).

WhenthescoresofHAD-AandHAD-Dwereevaluatedtogether withthegroup-familytype,thescoreofHAD-Dwasfoundtobe affectedbythefamilytypeinGroup2(p=0.009);thedepression scoreofthecoupleslivingwithinanuclearfamilywasdetected highercomparedtothecoupleslivingwithinatraditionalfamily (meanSD; 10.712.66 vs. 5.502.12) (F=5.390, p=0.021). HAD-A scores did not differ significantly between the group-familytypes(p>0.05).

Discussion

The present study was designed toinvestigate the effect of previous IVF-failure on the fertility-specific quality of life and emotionalstatusofthecouplesundergoingIVFtreatment,andit wasoneofthefirstsinthisareaaccordingtoourliteraturesearch. Studiesthatevaluatethefertility-specificqualityoflifeininfertile patients have recently gained great importance. In a study by Huppelschotenetal.,conductedwithinfertilecouplesin2013,the qualityoflife,particularlyinfemales,wasreportedtobeaffectedto a higher extent compared to their partners [26]. Similarly, Kahyaogluetal.demonstratednegativecorrelationofthe mind-body, tolerabilityand thetotal scoresof the FertiQoL withthe numberofunsuccessfulIVFattemptsininfertilewomen[27].

Table2

ComparisonofFeriQoL,HADanxietyanddepressionscoresofthecouplesingroups withandwithouthistoryofIVFfailure.

Group1(n=120) Group2(n=94) pValue Mean(SD) Mean(SD) CoreFertiQoL Emotional 59.51(20.39) 63.07(19.25) 0.19 Mind/body 67.46(19.83) 71.01(21.93) 0.22 Relational 71.31(18.89) 73.44(23.29) 0.47 Social 63.75(17.92) 66.40(18.28) 0.29 TreatmentFertiQoL Environment 55.45(15.72) 47.16(23.68) 0.009* Tolerability 50.00(24.00) 49.40(26.56) 0.87 TotalFertiQoL 52.50(9.95) 52.92(11.40) 0.77 A 2.66(0.89) 2.63(0.94) 0.68 B 3.05(2.12) 2.63(0.93) 0.71 HAD-A 10.73(3.31) 9.86(3.33) 0.06 HAD-D 9.98(2.73) 10.60(2.75) 0.10 Group1;coupleswithhistoryofIVFfailure;Group2;coupleswithouthistoryofIVF failure.

*

Statisticallysignificant, _Independentt-test.

Table3

MultilevelmultivariateanalysisofFertiQoLscoresaccordingtogroupsandothervariables.

Wilks’l F H_IPOTES_ISdf Erordf pValue Parsieletasquare

Gender-group 0.982 0.629 6 205 0.70 0.018 Age-group 0.956 0.766 12 406 0.69 0.022 Durationofinfertility-groupa _{0.921 2.926 6 205 0.009}* _0.079 Educationalstatus-group 0.915 1.525 12 404 0.11 0.043 Employmentstatus-group 0.987 0.441 6 205 0.85 0.013 Incomelevel-groupb 0.853 2.794 12 406 0.001* 0.076 Familytype-group 0.970 1.058 6 205 0.39 0.030 Causeinfertility-group 0.892 0.948 24 684 0.54 0.028 Wilks’l=pooledratiooferrorvariancestoeffectvariancepluserrorvariance.

H_IPOTES_ISdf;degreesoffreedomforthehypothesis.

Parsieletasquare;theratioofvarienceaccountedforbyaneffectandthateffectplusitsassociatederrorvarience.

a

ThehigherscoresweredetectedinenvironmentandtolerabilitydomainsubscaleoftheFertiQoLincoupleswithdurationofinfertilitylessthanfiveyearscomparedto theoneswith5yearsoraboveinGroup2(meanSD;53.362.75vs.39.483.42;p=0.003andmeanSD;54.443.46vs.43.553.85;p=0.044respectively).

b

Theenvironmentandtolerabilitysubscalescoresofthecoupleswithlowincomewerelowercomparedtothecoupleswithmiddleandhighincome(meanSDforthe environment subscale,10.863.12 vs. 52.612.82 and 42.473.90; p=0.006, and for the tolerability subscale,18.752.33 vs. 55.083.21 and 42.544.4; p<0.0001respectively)inGroup2.

* _{Statisticallysignificant,Multilevelmultivariateanalysis.}

Table4

MultilevelmultivariateanalysisofHADscoresaccordingtogroupsandothervariables.

Wilks’l F H_IPOTES_ISdf Erordf pValue Parsieletasquare

Gender-group 0.994 0.683 2 209 0.51 0.006 Age-group 0.967 1.747 4 414 0.14 0.017 Durationofinfertility-groupa 0.939 6.777 2 209 0.001* 0.061 Educationalstatus-groupb 0.958 4.593 2 208 0.011* 0.042 Employmentstatus-group 0.995 0.553 2 209 0.58 0.005 Incomelevel-group 0.981 1.013 4 414 0.40 0.010 Familytype-groupc 0.956 4.858 2 209 0.009* 0.044 Causeinfertility-group 0.946 1.420 8 400 0.19 0.028 Wilks’l=pooledratiooferrorvariancestoeffectvariancepluserrorvariance.

H_IPOTES_ISdf;degreesoffreedomforthehypothesis.

Parsieletasquare;theratioofvarienceaccountedforbyaneffectandthateffectplusitsassociatederrorvarience.

a

DepressionscoresdetectedlowerincoupleswithinfertilitydurationofbelowfiveyearsinGroup1(MeanSD10.402.89vs.9.492.45),whereaslowerdepression scoresweredetectedinthecoupleswithdurationofinfertilitylessthan5yearsinGroup2(meanSD9.802.64vs.11.592.58;p<0.0001).

b _{HAD-Dscoresdetectedhigherincaseswitheducationallevelbelowhigh-schoolcomparedtotheuniversitygraduatesinGroup2(meanSD;11.272.59vs.9.662.72;}

p=0.009).

c_{HAD-Dofthecoupleslivingwithinanuclearfamilywasdetectedhighercomparedtothecoupleslivingwithinatraditionalfamily(meanSD;10.712.66vs.}

5.502.12;p=0.021)inGroup2.

*

In thepresent study, it was shown that the coupleswith a history of IVF failure were less affected from the treatment environmentwhencomparedtothecoupleswithoutIVFfailure history.IncontrasttothefindingsofKahyaogluetal.ininfertile females, we determined that the mind-body and tolerability subscalesandtotalscoreofthefertility-specificqualityoflifedid not differ between the groups [27]. The only difference was originated from the environment subscale of the treatment section,andhigherenvironmenttolerabilityscoresweredetected inIVFfailuregroup.Thismaybeexplainablebythebeingfamiliar withthe treatment steps from the previouscycle or withthe increased desire of couples despite IVF-failure history which probablyincreasedthetolerabilityofthetreatment.

Inthisstudy,durationofinfertilityandincomelevelwasfound tohaveaneffectonqualityoflife.Howeverbothofthevariables affected the environment scores only in the couples without historyofIVFfailure.Wedeterminedthattheincreaseinduration of infertility and lowerincome level leadsdeterioration in the couples’ acceptances of the therapeutic approach and their orientationtothetherapy.Weconsiderthat thisresult maybe originatedfrombeinginexperiencedinthetreatment,feelingof intimidationinthefirstIVFattempt,andtheincreaseddurationof infertility probably decreasing tolerability with the increased durationofinfertilitydeterioratestheenvironmentscoresfurther. On the other hand, despite having an unsuccessful result previously, being familiar with the treatment steps makes it easierfor thecouples toorient tothe treatmentenvironment. Similarly,Ragniet al. alsoreporteddecreased the physicaland psychologicalscoresofthequalityoflifewithincreaseddurationof infertility,butdifferentfromourstudytheypreferredanonspecific generalhealthmeasurementtool(Healthsurveyshortform-36)in theirstudy[18].

Theenvironmentscoresinthecoupleswithalowincomewere foundtobemoreaffectedonlyinthegroupundergoingthefirstIVF therapy. The existence of economic problems, the cost of the medicationsusedininfertilitytreatment,expensesinthehospital andtheothercausesmaybeconsideredtoreducethephysicaland emotional tolerance of patients to the IVF therapy. Therefore, socioeconomiclevelseemsasanotherfactorleadingtodifferences inenvironmentscoresbetweengroups,asdoesthedurationof infertility.

Inourstudy,nodifferencesweredeterminedbetweengroups regardingthesociodemographiccharacteristics,exceptthelevelof education, socioeconomic status and the family type. The educational level and socioeconomic status were significantly higherinthecoupleswithpreviousIVF failure.Howeverinthe multivariateanalysis,wedeterminedthatthesecharacteristicshad noeffect on thequality of life in thecouples with IVF failure history.Ahigherlevelofeducationusuallyassociatedwithahigher levelofincomeandsocioeconomicstatusinsociety,andpotential associationofthesetwofactorsmaybeexplanationforthelossof importanceinmultilevelmultivariateanalysismodel.Accordingto currentliterature,theeffectofeducationonqualityoflifewasabit confusing. Karabulut et al. reported that orientation to the treatment environment in the quality of life scale was better fortheinfertilewomenwithahigheducationallevel,butthetotal scoresofthequalityoflifeandtolerabilityoftreatmentwerenot foundtobebetter.Theyconcludedthatinfertilityintenselyaffected theemotionalstatusandgeneralwell-being,andahighlevelof educationwasnotsufficienttomakethissituationmoretolerable

[11].Huppelschotenetal.detectedbetterQoLingroupwithhigh levelofeducationcomparedwithmoderateandlowlevels[26],but Chachamovich et al. reported lower environment scores of the qualityoflifeinpatientswithhighereducationlevel[14].

In thisstudy,wedetectednodifferenceforHADanxietyand depressionscoresbetweengroupswithand withoutIVFfailure.

However when we analyzed the groups together with the sociodemographic variables, IVF failure group revealed higher depressionscores,ifdurationofinfertilitywaslessthan5years.On contrary, group without IVF failure revealed lower scores, if duration of infertility was less than 5 years. Disappointment experiencedinthepre-treatmentperiodisprobablymuchmore intenseatthebeginningbutbythetimecouplesusuallyusedtothe situationandtheeffectbecomelessintense.Ontheotherhand,in thecouplesundergoingfirsttimeIVFtreatment,higherdepression scoreswithincreaseddurationofinfertilitymaybetriggeredby theincreaseddesireofhavingababywithincreaseddurationof infertility.Therefore,thesetwogroupsmayrequirepsychological supporteveniftheydonotdemandit,whichmaybehelpfulto increase quality of life and cooperation to the treatment. In accordance with this idea, Seyedi et al. screened females undergoing infertility treatment, and reportedimprovement in lifesatisfactionwithpositivepsychotherapyinthoseshowingmild tomoderatedepressivesymptoms[28].Theresultsofthisstudy seempromising,buttheycouldnotobtainany improvementin qualityoflifewhichmaybebecauseofthelimitedsamplesizeor theuseofnon-specificqualityoflifemeasurementtool.Therefore, further well designed studies with larger sample size were requiredtoclarifythesituation.

Inpreviousstudies,itwasreportedthat11.8%offemalesshow depressivesignspriortoIVFtreatment,andthisvalueroseto25.4% followinganunsuccessfulIVFattempt[29],andfemalesexpressed twofold moredepressivesignscompared tomales[30].In our study,wedonotperformevaluationaccordingtogender,instead evaluated as couple, but no gender effect was detected on depression scores of the couples in both groups in multilevel multivariateanalysis.

Wealsodetectedhighdepressionscoresinpatientswithlow education level in Group 2, but not in the IVF failure group. Similarly,Noorbalaetal.alsodetectedhigherdepressionscoresin infertilefemaleswithlowlevelofeducation[30].Problemsolving skillsareimportanttocopewithstressfulsituationwhichwere highlyrelatedwitheducationalstatus[31].IntheGroup2witha loweducationlevel,theperceptionsabouttheproceduresinthe courseofIVFtherapymayleadtoelevatedscoresofdepression.On theotherhand,havingapreviousexperienceaboutthetherapy mighthelptodevelopcopingstrategiesforeventheloweducated participantsintheIVFfailuregroup.

In the evaluation of the HAD scale, the type of family was another variablethat affected the depression scores. Karabulut etal. reportedlowerneedfor psychologicalsupportinpatients with extended families despite lower emotional scores [11]. Furthermore, Vasaard et al. showed decreasing effect of social supportoninfertilityrelatedanxietyanddepression[32].Inour study,depressionscoresweredetectedhigheramongthecouples livingwithinanuclearfamily.Thisresultmaybeexplainedbythe situation of not sharing problems in the nuclear family, and supportiveapproachintheextendedfamilies.Incontrasttothese results, Noorbala et al. reported that the comments of family membersaboutinfertilityinthecaseofextendedfamilyarethe maincausesofdepressionin81.3%ofthecouples[33].Therefore, the result may change according to the type of approach (supportive vs. humiliating etc.) that other family members expressedintheextendedfamilies.Although,afewculturalbased differencesinfertilityspecificqualityoflifebetweenthecouples definedinapreviousstudycomparingthreedifferentcultures,it requiresfurthercomparativestudiesindifferentculturestomakea morepreciseconclusionaboutthesubject[34].

Themainlimitationofourstudywasoriginatedfromlimited samplesizewhich canbeminimizedbymulti-centered studies withincreasednumberofparticipantsorthelongerenrollment periods.Thesecondlimitationwasoriginatedfromthemultiple

comparisonsperformedinthestudy.Wecouldnoteliminatesome degreeofchancefactororiginatedfromthenatureofthiskindof studies. However our study is important to emphasize that infertilityisnotadiseaserequiringonlythephysicalandmedical treatment,butalsorequiringapsychologicalapproach.Ourstudy thereforehighlightstheimportantpoints,andshedlighttomore advancedstudiesconductedonthissubject.

In conclusion, fertility-specific quality of life scores reveals betterresultsregardingtheorientationtothetreatment environ-mentinthecoupleswithapreviousIVFfailure,comparedtofirst IVFcyclecouples.Treatmentfailuredoesnotelevatethelevelof anxiety,whiletheeffectondepressionscoreschangesaccordingto durationofinfertility.

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[1]Zegers-HochschildF,AdamsonGD,de MouzonJ, etal. TheInternational CommitteeforMonitoringAssistedReproductiveTechnology(ICMART)and theWorldHealthOrganization(WHO)RevisedGlossaryonARTTerminology. InternationalCommitteeforMonitoringAssistedReproductiveTechnology; WorldHealthOrganization.HumReprod2009;24:2683–7.

[2]BoivinJ,TakefmanJ,BravermanA.Thefertilityqualityoflife(FertiQoL)tool: development and general psychometric properties. Hum Reprod 2011;26:2084–91.

[3]Kraft AD, Palombo J, Mitchell D, Dean C, Meyers S, Schmidt AW. The psychologicaldimensionsofinfertility.AmJOrthopsychiatry1980;50:618–28. [4]ÖzçelikB,Karamustafaoglu,ÖzçelikA. _Infertiliteninpsikolojikvepsikiatrik yönü(Psychologicalandpsychiatricaspectsofinfertility).Anadolupsikiatri Dergisi(AnatoliaPsychiatriJ)2007;8:140–8.

[5]CousineauTM,DomarAD.Psychologicalimpactofinfertility.BestPractRes ClinObstetGynaecol2007;21:293–308.

[6]Aarts JW, van Empel IW, Boivin J, Nelen WL, Kremer JA, Verhaak CM. Relationshipbetweenqualityoflifeanddistressininfertility:avalidation studyoftheDutchFertiQoL.HumReprod2011;26:1112–8.

[7]HerediaM,TeníasJM,RocioR,AmparoF,CallejaMA,ValenzuelaJC.Qualityof lifeand predictive factors in patients undergoing assisted reproduction techniques.EurJObstetGynecolReprodBiol2013;167:176–80.

[8]DomarAD,BroomeA,ZuttermeisterPC,SeibelM,FriedmanR.Theprevalence andpredictabilityofdepressionininfertilewomen.FertilSteril1992;58: 1158–63.

[9]GourountiK,Anagnostopoulos F,PotamianosG, Lykeridou K,SchmidtL, VaslamatzisG. Perception ofcontrol, copingand psychological stressof infertilewomenundergoingIVF.ReprodBiomedOnline2012;24:670–9. [10]VerhaakCM,Smeenk JM,EversAW,KremerJA,KraaimaatFW,BraatDD.

Women’semotionaladjustmenttoIVF:asystematicreviewof25yearsof research.HumReprodUpdate2007;13:27–36.

[11]KarabulutA,ÖzkanS,OguzN.Predictorsoffertilityqualityoflife(FertiQoL)in infertilewomen:analysisofconfoundingfactors.EurJObstetGynecolReprod Biol2013;170:193–7.

[12] ChachamovichJ,ChachamovichE,FleckMP,CordovaFP,KnauthD,PassosE. Congruenceofqualityoflifeamonginfertilemenandwomen:findingsfroma couple-basedstudy.HumReprod2009;24:2151–7.

[13]TestaMA,SimonsonDC.Assesmentofquality-of-lifeoutcomes.NEnglJMed 1996;28(334):835–40.

[14]ChachamovichJR,ChachamovichE,ZachiaS,KnauthD, PassosEP.What variablespredictgenericandhealth-relatedqualityoflifeinasampleof Brazilianwomenexperiencinginfertility?HumReprod2007;22:1946–52. [15]Menning BE. The emotional needs of infertile couples. Fertil Steril

1980;34:313–9.

[16]RashidiB,MontazeriA,RamezanzadehF,ShariatM,AbediniaN,AshrafiM. Health-related quality of life in infertile couples receiving IVF or ICSI treatment.BMCHealthServRes2008;19(8):186.

[17]JohanssonM,AdolfssonA,BergM,etal.Qualityoflifeforcouples4–5.5years afterunsuccessfulIVFtreatment.ActaObstetGynecolScand2009;88: 291–300.

[18]RagniG,MosconiP,BaldiniMP,etal.Health-relatedqualityoflifeandneedfor IVFin1000Italianinfertilecouples.HumReprod2005;20:1286–91. [19]FertiQoL.2012.Avaliableat:http://www.fertiqol.org[accessed26.12.12]. [20]DomarAD,SiebelMM.Emotionalaspectofinfertility.In:SiebelMM,editor.

Infertility:acomprehensivetext.Stamford:Appleton&Lange;1997.p.29–44. [21]MeyersM,DiamondR,KezurD,ScharfC,WeinshelM,RaitDS.Aninfertility primerforfamilytherapists:I.Medical,social,andpsychologicaldimensions. FamProcess1995;34:219–29.

[22]CwikelJ,GidronY,SheinerE.Psychologicalinteractionswithinfertilityamong women.EurJObstetGynecolReprodBiol2004;117(December(2)):126–31. [23]DomarAD,ZuttermeisterPC,SeibelM,BensonH.Psychologicalimprovement

ininfertilewomenafter behavioral treatment:areplication. FertilSteril 1992;58:144–7.

[24]WorldHealthOrganization.Recentadvancesinmedicallyassisted reproduc-tion.WHOtechnicalreportseries820.Geneva:WHOPublications;1992. [25]AydemirÖ,GüvenirT,KüeyL,KültürS.Hastaneanksietevedepresyonölçegi

Türkçeformunungeçerlilikvegüvenilirligi(TurkishvalidationofHoaspital anxiety and depression scale).Türk Psikiatri Dergisi (Turk Psychiatri J) 1997;8:280–7.

[26]HuppelschotenAG,vanDongenAJ,VerhaakCM,SmeenkJM,KremerJA,Nelen WL.Differencesinqualityoflifeandemotionalstatusbetweeninfertile womenandtheirpartners.HumReprod2013;28:2168–76.

[27]KahyaogluSutH,BalkanliKaplanP.Qualityoflifeinwomenwithinfertilityvia theFertiQoLandtheHospitalAnxietyandDepressionscales.NursHealthSci 2014(September),doi:http://dx.doi.org/10.1111/nhs.12167.

[28]Seyedi AslST, SadeghiK, BakhtiariM, Ahmadi SM,Nazari AnamaghA, KhayatanT.Effectofgrouppositivepsychotherapyonimprovementoflife satisfaction and thequality oflifein infertilewoman.Int JFertil Steril 2016;10:105–12.

[29]NewtonCR,HearnMT,YuzpeAA.Psychologicalassessmentandfollow-up afterinvitrofertilization:assessingtheimpactoffailure.FertilSteril1990;54 (November(5)):879–86.

[30]NoorbalaAA,RamazanzadehF,MalekafzaliH,etal.Effectsofapsychological intervention on depression in infertile couples. Int J Gynaecol Obstet 2008;101:248–52.

[31]SchmidtL,ChristensenU,HolsteinBE.Thesocialepidemiologyofcopingwith infertility.HumReprod2005;20:1044–52.

[32]VasaardD,LundR,PinborgA,BoivinJ,SchmidtL.Theimpactofsocialrelations amongmenandwomeninfertilitytreatmentonthedecisiontoterminate treatment.HumReprod2012;27:3502–12.

[33]NoorbalaAA,RamezanzadehF,AbediniaN,BagheriSA,JafarabadiM.Studyof psychiatricdisordersamongfertilinfertilewomenandsomepredisposing factors.JFamReprodHealth2007;1:6–11.

[34]SextyRE,HamadnehJ,RösnerS,etal.Cross-culturalcomparisonoffertility specificqualityoflifeinGerman,HungarianandJordaniancouplesattendinga fertilitycenter.HealthQualLifeOutcomes2016;14:27.