InfertilityInfertility

• EpidemiologyEpidemiology

• Overview of fertility treatmentsOverview of fertility treatments

Infertility OverviewInfertility Overview

• EpidemiologyEpidemiology• Natural conceptionNatural conception• IncidenceIncidence• CausesCauses

• InvestigationInvestigation• WhenWhen• Which testsWhich tests

Key stepsKey steps

Infertility - incidenceInfertility - incidence

• Incidence Incidence • population based studiespopulation based studies• 24 months unprotected intercourse24 months unprotected intercourse• 1:6 overall1:6 overall

• Subfertility • Azoospermia (No sperm)• ovarian failure (No oocytes)• extensive tubal damage (Gametes cannot

meet)

Cumulative conceptionCumulative conception

• Normal couples prospect of conceptionNormal couples prospect of conception

• 33% first month33% first month• 20-25% thereafter20-25% thereafter

• 84% conceive by 1 year84% conceive by 1 year• 92% by 2 years92% by 2 years

Causes of infertility - diagnosisCauses of infertility - diagnosis

Cause Frequency (%) 

Sperm dysfunction 30 

Ovulation failure 25 

Tubal infective damage 20 

Unexplained 25 

Endometriosis 5 

Infertility investigationsInfertility investigations - general - general adviceadvice

• Check Rubella immunity Check Rubella immunity (female)(female)

• Smoking Smoking (both)(both)

• AlcoholAlcohol• Folic acid Folic acid (female)(female)

• 0.4mg/d0.4mg/d (reduces risk of spina bifida)(reduces risk of spina bifida)

• Weight Weight (female)(female)

• BMI <30BMI <30• Kg/m2Kg/m2

Infertility investigations - primary careInfertility investigations - primary care

• Develop local protocolsDevelop local protocols• evidence basedevidence based

• MaleMale• SFA x 2SFA x 2

• FemaleFemale• midluteal progesteronemidluteal progesterone

• >30nmol/l>30nmol/l

Infertility investigations - lack of Infertility investigations - lack of evidenceevidence

• Not recommended routinelyNot recommended routinely

• Thyroid functionThyroid function• ProlactinProlactin• PCT/Sperm function testsPCT/Sperm function tests• Endometrial biopsy or scanEndometrial biopsy or scan• HysteroscopyHysteroscopy

When to refer early from primary careWhen to refer early from primary care

• Female factorsFemale factors

• age > 35 yrs age > 35 yrs (biological clock)(biological clock)

• Oligo/amenorrhoeaOligo/amenorrhoea

• Previous pelvic Previous pelvic surgerysurgery

• PID/STDPID/STD

Numbers of oocytes with ageNumbers of oocytes with age

0 20/40 Birth Puberty 25 4535

7 million

Parameter Value

Volume

2-6ml

Sperm density >20m/ml

Sperm motility >50%

Sperm morphology (Kruger)

>15%

Morphology best indicator of sperm function but combined defects more important

Seminal Fluid AnalysisSeminal Fluid Analysis

Sperm dysfunctionSperm dysfunction• History / ExaminationHistory / Examination

• genitourinary surgerygenitourinary surgery• undescended testisundescended testis• mumpsmumps

• InvestigationInvestigation• SFA SFA • Azoospermia (check karotype)Azoospermia (check karotype)

• Spontaneous conception Spontaneous conception • possiblepossible• 20% over 2 yrs20% over 2 yrs

• ICSIICSI• 30%/cycle30%/cycle

Ovulation Ovulation

• Physiological indicators of Physiological indicators of ovulationovulation• Cervical mucus thins and Cervical mucus thins and

increasesincreases• mid cycle pain (mittleschmertz)mid cycle pain (mittleschmertz)• Rise in basal body temperatureRise in basal body temperature

• History suggestive of History suggestive of anovulationanovulation• infrequent / absent periodsinfrequent / absent periods• >35 days apart>35 days apart• Mid luteal progesterone Mid luteal progesterone

(<30mmol/l)(<30mmol/l)Day 21

0 28

Failure of OvulationFailure of Ovulation

• AnovulationAnovulation• PPolyolyCCystic ystic OOvarian varian SSyndrome yndrome

(PCOS)(PCOS)

• HyperprolactinemiaHyperprolactinemia• drugsdrugs• stressstress• pituitary tumorpituitary tumor

• Premature ovarian failurePremature ovarian failure• 1% <40 yrs1% <40 yrs• 0.1% <30 yrs0.1% <30 yrs

• HypothalamicHypothalamic• Low GnRH driveLow GnRH drive

Undesired hair growth

Anovulation – managementAnovulation – management

• PCOSPCOS• ClomifeneClomifene• MetforminMetformin• FSH injectionsFSH injections• Ovarian drillingOvarian drilling

• HyperprolactinaemiaHyperprolactinaemia• dopamine agonist (bromocriptine)dopamine agonist (bromocriptine)• inhibits prolactin secretioninhibits prolactin secretion

• Premature ovarian failurePremature ovarian failure• IVF donated oocytesIVF donated oocytes

• Hypothalamic causesHypothalamic causes• GnRH pumpGnRH pump

Tubal infective damageTubal infective damage

• AetiologyAetiology• Chlamydia trachomatis commonest Chlamydia trachomatis commonest

• Silent carriageSilent carriage• Age <25 yr incidence increasingAge <25 yr incidence increasing• TOP (7.5%)TOP (7.5%)• 20-24yr (11.5%)20-24yr (11.5%)

• HistoryHistory• nonenone• Pelvic Inflammatory Disease (PID)Pelvic Inflammatory Disease (PID)• infective complications following pregnancyinfective complications following pregnancy

• DiagnosisDiagnosis• Hystero-SalpingoGram (HSG) or Hycosys Hystero-SalpingoGram (HSG) or Hycosys (screen)(screen)

• laparoscopylaparoscopy

Laparoscopy Female Anatomy

Bladder

Vagina

Uterus

Ovary

Rectum

Tubal infertilityTubal infertility - hydrosalpinx - hydrosalpinx

• Offer salpingectomy if hydrosalpinx present (NICE)

Tubal infective damage - managementTubal infective damage - management

• Tubal surgeryTubal surgery• major operationmajor operation• limited success (20%)limited success (20%)• ectopic pregnancy ectopic pregnancy

• Removal of tubeRemoval of tube• Potentially seriousPotentially serious

• IVFIVF• expensiveexpensive• complicationscomplications• success rates depend success rates depend

on female age (30%)on female age (30%)

Cumulative conception in unexplained Cumulative conception in unexplained infertilityinfertility

0

10

20

30

40

50

60

70

80

6 12 18 24

months

Percent couples1 to 3 yrs

> 3yrs

Unexplained infertilityUnexplained infertility - management - management

• WaitWait

• <3 years<3 years• reasonable prospect of conceptionreasonable prospect of conception

• >3 years>3 years• IVF observe fertilisation occurring IVF observe fertilisation occurring • IUI (intrauterine insemination)IUI (intrauterine insemination)

• Female age importantFemale age important

EndometriosisEndometriosis

• What is it ?What is it ?• Endometrial cells at sites Endometrial cells at sites

outwith the uterusoutwith the uterus• OvaryOvary• PelvisPelvis• Bowel/bladderBowel/bladder• LungsLungs

• AetiologyAetiology• ? retrograde menses? retrograde menses• Familial associationFamilial association• EmbolisationEmbolisation• Immunological Immunological

Female Anatomy

Bladder

Vagina

Uterus

Ovary

Rectum

EndometriosisEndometriosis

• HistoryHistory• pelvic painpelvic pain• Dysmenorrhoea Dysmenorrhoea • deep dyspareuniadeep dyspareunia

• DiagnosisDiagnosis• LaparoscopyLaparoscopy

• Why does it reduce fertility ?Why does it reduce fertility ?• ? Sperm function? Sperm function• ? Tubal motility? Tubal motility• ? Oocyte quality? Oocyte quality

Endometriosis - managementEndometriosis - management

• Laser or diathermy Laser or diathermy • improves conception improves conception

ratesrates

• If pelvis anatomically If pelvis anatomically distorted distorted • IVFIVF• laser to ovarian cystslaser to ovarian cysts

Intrauterine inseminationIntrauterine insemination

• IndicationsIndications• UnexplainedUnexplained• Mild male factorMild male factor

• 2y infertility2y infertility• Minor endometriosisMinor endometriosis

• Tubal patency Tubal patency

• Natural cycleNatural cycle• NICE guidance 6 unstimulated NICE guidance 6 unstimulated

cyclescycles• Stimulated cycleStimulated cycle

• ClomifeneClomifene• FSH injectionsFSH injections• Multiple pregnancyMultiple pregnancy

Indications for IVF/ICSIIndications for IVF/ICSI

• IVFIVF• TubalTubal• Prolonged unexplainedProlonged unexplained• Severe endometriosisSevere endometriosis• Unexplained failure of ovulation inductionUnexplained failure of ovulation induction

• ICSIICSI• Severe male factorSevere male factor• Failed ferilisation with IVFFailed ferilisation with IVF

In vitro fertilisation (IVF)In vitro fertilisation (IVF)

• Pituitary densitisation (GnRHa nasal Pituitary densitisation (GnRHa nasal spray)spray)

• Stops ovulationStops ovulation

• Ovarian hyperstimulation Ovarian hyperstimulation (daily FSH (daily FSH injections)injections)

• Multiple follicles and eggsMultiple follicles and eggs

• Egg retrievalEgg retrieval• Sedation TVUSSSedation TVUSS

• Embryo transferEmbryo transfer• Max 2 embryos (UK) Max 2 embryos (UK)

• Luteal supportLuteal support• Progesterone pessariesProgesterone pessaries

• IssuesIssues• Welfare of the ChildWelfare of the Child• Multiple pregnancy ratesMultiple pregnancy rates• Success ratesSuccess rates• NHS fundingNHS funding

• 3 cycles3 cycles• Age 23-39Age 23-39• criteriacriteria

Long GnRHa

21

0

12Cycle day

IVF Stimulation cycle - overview

Menses

OR ET

Daily FSH injections

hCG

Luteal support

Risks in ART cycleRisks in ART cycle

Poor ovarian responsePoor ovarian response

Ovarian hyperstimulation Ovarian hyperstimulation syndromesyndrome• iatrogenic• PCOS• pregnancy

Multiple pregnancyMultiple pregnancy• move to elective single

embryo transfer

Impact of female age and basal FSH on IVF livebirth Impact of female age and basal FSH on IVF livebirth

raterate ((Akande et al 2002)

0

5

10

15

20

25

30

1979 1989 1999 2009

Proportion of all pregnancies to Proportion of all pregnancies to women >35 yearswomen >35 years

Can ART (IVF) compensate for the natural decline in

fertility with age? Leridon 2004

• Computer Model of Reproduction• Combined

• the monthly probabilities of conceiving• the risk of miscarriage

• probability of becoming age-dependently permanently sterile

• Delay 30 to 35 years• IVFIVF• Makes up for 50% of age related lossesMakes up for 50% of age related losses

• Delay 35 to 40 years• Makes up for <30%Makes up for <30%

• More precise information required about risks of postponing childbirth

Infertility investigations - summaryInfertility investigations - summary

• Common condition Common condition (1:6)(1:6)

• Sperm dysfunctionSperm dysfunction• SFASFA

• AnovulationAnovulation• historyhistory• midluteal progesteronemidluteal progesterone

• TubalTubal• HSG Hycosys or laparoscopyHSG Hycosys or laparoscopy

• EndometriosisEndometriosis• laparoscopylaparoscopy

• UnexplainedUnexplained• all of above are normalall of above are normal

Infertility treatment - summaryInfertility treatment - summary

• Sperm dysfunctionSperm dysfunction• Mild IUIMild IUI• Severe ICSISevere ICSI

• AnovulationAnovulation• PCOSPCOS

• ClomifeneClomifene• MetforminMetformin• FSH injections or Ovarian diathermyFSH injections or Ovarian diathermy

• HyperprolactinaemiaHyperprolactinaemia• Bromocriptine/cabergolineBromocriptine/cabergoline

• Ovarian failureOvarian failure• IVF Donor eggsIVF Donor eggs

• TubalTubal• Surgery (mild)Surgery (mild)• IVFIVF

• EndometriosisEndometriosis• ablation improvesablation improves• IUI or IVFIUI or IVF

• UnexplainedUnexplained• Wait IUI IVFWait IUI IVF

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