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Update on Prevention and Management of Infertility for Primary Care*

 

Clare Boothroyd

Medical Director

Assisted Conception Australia

1 May 2011

 

Postcards from the Edge, Gold Coast Convention Centre

 

www.acaivf.com.au

 

Past public education campaign to reduce infertility

American Fertility Society conducted a public education campaign to reduce the prevalence of infertility, addresssing 4 key areas – age, sexually transmitted infection, unhealthy body weight and smoking as – four potential areas of behaviour which were modifiable and would result in reduction of the suffering of infertilty.

 

The AFS spent US$50,000 - ads in buses, 30 second radio announcements, no TV, brochures on mail or internet in New York, Chicago, Seattle

Planned 2001 launch

Newsweek wanted exclusive “earned media” coverage

RESOLVE supportive statements

“careers vs family”  National Organization for Women adopted antagonist role  - ad encouraging women to have babies before they are ready and “hidden agenda” of lucrative fertility industry

ACOG declined to support because “anti breastfeeding”

Some negative letters from infertility patients

Sylvia Hewlett “Creating a life - Professional Women and the quest for children”

Silver Screen Media declined to show ads in theatre “lacking entertainment value”

Continued until 2002

$150,000 excellent earned media coverage - controversy  abounded.

 

 

The rise and rise of assisted reproduction

July 25 1978

Louise Brown born

First IVF baby

Born to Lesley Brown, bilateral tubal blockage

Natural cycle, single egg fertilization

HISTORY OF IVF

1878 - first reported attempts at IVF

1959 - IVF births in rabbits in USA

1968 - first human IVF (Edwards, Bavister)

1978 - Birth of first IVF baby (Steptoe, Edwards)

1992 - Birth of first baby after ICSI     (intracytoplasmic sperm injection) (Palermo)

 

ART in Australia during 2003

36,040 treatment cycles conducted

6474 babies were born in Australia

more than half the cycles use microinjection/ICSI

ART in Australia 2008

61,000 IVF/ICSI cycles  (Wang et al 2008 NPSU)

~15,000 babies born

One child in every classroom is from ART and set to rise

 

Fertility preservation/ reproductive life planning is now essential

                                                             

Prevention of infertility

1.Deferral – age related

2.Sexually transmitted infection

3.Smoking

4.Unhealthy body weight – too low, too high

 

Age related

Dunson et al 2002 show that if the male is 5 or more years older than the female at age 35-39 their fecundability is lower than if the male is the same age as the female or younger.

Possible reasons for declined fecundity with paternal age (controlled for maternal age and coital timing, frequency) are

·         Genetic defects of sperm increase with age

·         FSH rises with age  ?age related change in pituitary gonadal axis

·         No definite seminal parameter changes

·         Morphological changes e.g. prostate changing seminal quality

Paternal age and maternal age increase risk of miscarriage

Miscarriage increases as maternal age increases

Controlling for maternal age, risk of miscarriage increases as paternal age increases

(Dela Rochebrocard & Thonneau HR 2002:17:1649)

Our STI incidence

Predictors of STI - USA

survey of 9882 sexually active women 1995

reported STI (C. trachomatis, N. gonorrhoea) and PID

Coitarche 18 yrs - 5 times more likely to get STI, 2 times more likely to get PID

> 5 partners more than 10 times more likely to get STI

no protection from condoms (?confounder)

Miller et al, Fam Plan Perspectives  1999

Australian Study of Health and
Relationships

http://www.pha.org.au/anzjph/anzjph/2003

Telephone survey of 19,307 people aged 16-59

73% response rate

Questions: relationships, families, fertility, sexual experiences, use of condoms, contraception, sexual satisfaction and difficulties, sexual attitude and knowledge of sexually transmitted infections

APHS told us a lot about sexual experience in Australia

·         Prevalence of homosexuality

·         Mean no. of sexual partners

·         Frequency of coitus

·         Expectations of monogamy

·         Experience of commercial sex

·         Experience of coercion in sex

·         Sexual difficulties, pleasure, infertility

·         Median ages at first vaginal intercourse and first oral sex

·         Percentage of respondents who reported engaging in vaginal intercourse before age 16

Consequences of early coitarche

·         Increased number of sexual partners over life

·         Increased risk of STI

·         Increased risk of teenage pregnancy

·         Regret

Medical profession and safer (not safe) sex

Medical student awareness of sexual health is poor -Univ Bristol, internet survey - poor  knowledge about failure rates of condoms, chlamydial infection, TOP rates (Fayers et al, Int J STD AIDS 2003)

Safe sex behavioural questionnaire to 44 medical graduates and 44 law and other graduates -  high rates of unsafe sexual behaviours despite knowledge (Williams and Foebert Acad Psychiatry 2003)

Issues

Condom failure for pregnancy 2-15 per 100 women years

28% males had one condom breakage per year and 18% had condom slippage

Reduction in HIV use with condoms may not apply to highly infectious STIs such as gonococcus and chlamydia (Pinkerton et al, Int J STD AIDS 2003)

When to stop using condoms in a casual relationship which continues?

 

Australian Study of Health and
Relationships told us that Australian have

poor knowledge about transmission of STIs

·         1/5 have had a recognised STI at some time

·         2% have had STI in the last year

·         Levels of knowledge about STI in Australian adults

o   Evaluated by 10 questions in Australian Study of Health and Relationships

o   “Chlamydia can lead to infertility in women” - 34% of men gave a correct response and 57% of women gave a correct response

o   70% of both sexes believed that Chlamydia only affects women

Long term

Chlamydia epidemic in 15-25 year olds in combination with deferred childbearing = increased requirement for IVF in 10-20 years

How to reduce this is our national health challenge?

Influence of smoking

Smoking in women trying to conceive

Meta analysis of 12 studies smokers vs non smokers OR female infertility 1.6 (95%CI 1.34-1.91)  (Augood et al Hum Reprod 1998)

Meta analysis female smokers require twice as many IVF cycles to achieve a pregnancy (Feichtinger et al, J Assist Reprod Genet 1997)

Smokers on average have earlier menopause and reduced ovarian reserve

 

 

Smoking in men

No good evidence on seminal parameters in smokers

No good evidence of reduced fecundity in male smokers

Male smokers in IVF programme have half the success rate of male non-smokers.

 

 

Our obesity epidemic

Influence of weight on fertility

BMI at age 18 if greater than 25 predicts female infertility - RR 1.3 and RR>3 if BMI >32 regardless of PCOS or not (Rich-Edwards Am J Obstet Gynaecol 1994)

Low BMI predicts anovulation

BMI 25  predicts reduction in sperm quality (Jensen et al  Fertil Steril 2004)

BMI > 35 associated with OR 0.5 (0.32-0.77) in IVF (Wang et al  BMJ 2000)

 

Varicella vaccineRACGP Update 2011

Case 1

Non immune varicella

35 yrs

3 yrs infertility

Commencing IVF soon

Should varicella vaccine be administered?

If she was 38 yrs?  If she was 40 yrs?

Varicella in pregnancy

?  Varicella syndrome if <20 weeks gestation

?  Stillbirth, teratogenesis (skin scarring, limb hypoplasia, ocular brain defects)

?  12-28 weeks 1.5% syndrome

?  <12 weeks 0.5% syndrome

?  Nil after 28 weeks

?  Systemic varicella in neonate if first maternal infection at the time of delivery – indication for VIG

?  Severe systemic infection pneumonitis in pregnancy

VZV infection in Australia

125,000 cases annually

0.5%- 0.3% occur in women in reproductive age group (USA and UK estimates)

36 cases per year in Australia in pregnancy

RANZCOG

Screen for varicella immunity if no or uncertain history of chicken pox at time of ANC

If negative vaccinate after pregnancy

Varicella vaccine

Live attenuated Oka strain

Two doses 0.5mls 1-2 months apart

Avoid pregnancy for one month after second injection

Recommended for high risk (child care) and those having “expensive and invasive fertility treatment”  Casey et al 2008

“Varivax”™ pregnancy registry

Merck from 1995-2005

131 live births from seronegative women vaccinated 3months or less before pregnancy

3 birth defects (3.7%) and no congenital varicella syndrome

Wilson et al J Infect Dis 2008

 

 

Prevention of neural tube defects Folic acid vs multivitamin

Which is best to recommend?

            Folic acid

            Multivitamin without folic acid

            Multivitamin with folic acid

 

 

See www.cochrane.org.au

 

Folic acid vs placebo NTD
Lumley et al 2001

Folic acid vs multivitamins NTD
Lumley et al 2001

Folic acid vs folic acid and multivitamins

Iodine supplements in pregnancy

Epidemiologic evidence of reduced urine iodine excretion (marker of low intake) in Australia due to less use iodised salt and less iodine contamination of dairy products

Pregnant women have increased iodine requirements from 150 mcg per day to 250 mcg

From conception or early pregnancy

Outcome is reduced fetal hypothyroidism

 

 

See and download “Use of iodine in pregnancy” information sheet www.acaivf.com.au

 

 

Should TSH be an antenatal screening test?

Maternal hypothyroidism and the fetus

Identification of women with elevated TSH during pregnancy from stored samples

Tested children 9-11 years later

?Blinding of subjects ?Adjustment for confounders

62/25,216 women had high TSH in second trimester.  124 matched controls. Some women were treated during pregnancy

Haddow et al, New Engl J Med 1999

 

 

Maternal hypothyroidism and pregnancy outcome

1969  Man et al, Am J Obstet Gynecol

1999 Haddow et al New Engl J Med

2001 Pop et al Clin Endocrinol

All suggest reduced neuro-psychological performance

TSH as an antenatal screening test?

Prevalence high TSH 1.9/1000  ie 500 women screened  to detect one at risk fetus (Oats, MJA 2000)

Prevalence high TSH may be 2.5% in pregnancy (Klein, Clin Endocrinol 1991)

Hypothyroidism increases with age

Deferred childbearing, infertility -  selective screening indicated (cvb)

Male infertility

Increased risk of testicular cancer with semen abnormalities

Cohort study of 32,442 men in Denmark from 1965-1992 who had SFA

Correlate of testicular cancer (and extraperitoneal germ cell tumours) with SFA abnormality:

IR 1.6 (95%CI 1.3-1.9) constant over time from SFA

IR 2.3 oligospermia, 2.5 asthenoozospermia 3.0 teratoozospermia

Jacobsen et al  BMJ 2000

 

 

Testicular cancer

Peak incidence between 15 and 40 yrs

Usually present to primary care physicians

Risk factors:

Undescended testes  OR 4

Infantile hernia OR 2

SFA abnormality OR 1.6

Note orchidopexy <10 yrs reduces the risk

De Kretser BMJ 2000

 

 

Should we screen for testicular cancer by USS or just recommend TSE?

Uncertain

TSE routine recommendation

Opportunist USS e.g. at fertility clinic 6% have microlithiasis on USS of testis (Jecquier FSA 2008)

 

 

Male factor infertilityRACGP Update 2011

Increased risk of testicular cancer

Reversible male infertility ~<10%

If testicular damage, may be at risk of hypogonadism

Infertile men need medical review!!

 

* These notes are for those who attended the lecture at the 54th RACGP Clinical Update at the Gold Coast Convention Centre on 1st May 2011

 

 

 
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