Preparation for IVF
Ian Cooke
Emeritus Professor
University of Sheffield
Director of Education
International Federation of Fertility Societies
Precongress seminars
XIХ International conference of RAHR
“Reproductive technologies today and
tomorrow”
September, 10-12, 2009
Irkutsk, Siberia
Preparation for IVF
 Of the patients
 Of staff and facilities
 Of organisation
• Review of U.K. infertility Guideline
algorithm (2004, but valid)
• Emphasis on process leading to IVF
U.K. National
Guideline developed
by a multidisciplinary
group:
Stages
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are needed to see this picture.
1. Process published
2. Draft formulated
3. Professional
consultation
with interested
bodies
4.Modification
5. Final publication
Background
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The Guideline was produced for the NHS because of the wide
variation in and limited access to NHS treatment. It covered a new
review of the research evidence.
The National Institute for Clinical Excellence (NICE) Guideline was “to offer
best practice advice on the care of people in the reproductive age
group who perceive that they have problems in conceiving” (Feb.2004)
Based on the Management of Infertility (RCOG,1998-2000) :
initial (primary) investigation and management,
management in secondary care and
management in tertiary care.
The full Guideline (CG11, 500pp. with refs) “Fertility assessment and
treatment for people with fertility problems” is available (as a 1.21Mb
file) at:
http://www.nice.org.uk/guidance/index.jsp?action=download&o=29269
Grades of Evidence
LEVEL
EVIDENCE
GRADE
1a
Systematic review and meta-analysis of RCTs
A
1b
At least 1 (randomised controlled trial) RCT
At least one well-designed CT without
randomisation
At least one other type of quasi-experimental
study
Well-designed non-experimental descriptive
studies, such as comparative, correlation or
case-control studies
Evidence from expert committee reports or
opinions &/or clinical experience of respected
authorities
2a
2b
3
4
B
C
D
The view of the Guideline Development Group GPP
Algorithm for assessment and treatment
for people with fertility problems (NICE)
• Definition of infertility - 2 years
• Initial advice to people concerned about conception
• Early investigation
- history of predisposing factors
- woman’s age ≥ 35y
- HIV status
- hepatitis B & C
• People preparing for cancer treatment (oocyte cryopreservation)
• Principles of care
- Couple centred management
- Access to evidence-based information (verbal and written)
- Counselling from someone not directly involved in management
of the couple’s infertility
- Contact with fertility support groups
- Specialist teams
Initial advice -1
 Cumulative probability of pregnancy in
the general population
 Fertility declines with a woman’s age
• Lifestyle advice
 Preconceptual advice
-folic acid, rubella, cervical screening
Initial Advice - 2
• Intercourse at least every 2-3 days C
• Alcohol not >2-3U/day (F) D
not >3-4 U/day (M) GPP
excess alcohol is detrimental to semen quality B
• Smoking may reduce fertility in females, refer to cessation
programme A
• Smoking in males: no link, but stopping will improve
general health GPP
• Passive smoking may reduce fertility B
• No consistent evidence about caffeinated beverages (tea,
coffee, cola) B
• BMI ≥30 (F), if anovulatory, lose weight, preferably in a
group A
• BMI ≥30 (M) is likely to be associated with reduced fertility C
• BMI <18 with irregular menses should gain weight B
Clinical investigation and management
strategy for the male
Semen analysis (WHO)
If abnormal
If normal, see female /
unexplained infertility
Hypogonadotrophic
hypogonadism:
Mild male factor fertility problems:
 Gonadotrophins
Unstimulated IUI x 6 cycles
Obstructive azoospermia:
Surgery
Sperm recovery
Varicocele(s):
NO Surgery
Ejaculatory failure:
Drug therapy
IVF
Sperm recovery
IVF
IVF
Failure of
IUI IVF
Assessment of ovulation
• Day 21 Serum progesterone (may be later)
• Serum gonadotrophins, FSH and LH
• No prolactin, unless galactorrhoea or
pituitary tumour
• No inhibin B; no thyroid function tests
unless symptoms of thyroid deficiency
• No endometrial biopsy
Irregular ovulation
• WHO Group I
- gonadotrophins with LH activity
- pulsatile LH
• WHO Group II
- mainly PCOS
Clomiphene
- if anovulatory on clomiphene, hMG or
uFSH or rFSH with ultrasound
monitoring
Hyperprolactinaemia
-bromocriptine
Tests for tubal occlusion
• Semen analysis and ovulation data should
be known
• Screen for Chlamydia trachomatis before
uterine examination or prophylactic
antibiotics
• HSG or Hysterosalpingo-contrastultrasonography if no history of
endometriosis or pelvic inflammatory
disease or ectopic
• Laparoscopy and dye if history of co-morbidity
Female
Consider:
• If occlusion,
- IVF
- tubal surgery if mild disease
- tubal catheterisation or cannulation if proximal occlusion
• If minimal/mild endometriosis
- Surgical ablation or resection and adhesiolysis at laparoscopy
- If no pregnancy
- Stimulated IUI for 6 cycles with ultrasound monitoring
with risk of OHSS and multiple pregnancy
• If moderate/severe endometriosis
- surgery
• Endometriomas
- laparoscopic surgery
Unexplained infertility
• If normal:
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Unexplained infertility (normal
semen analysis, no ovulation
disorders, no tubal occlusion)
clomiphene citrate
unstimulated intrauterine insemination (IUI)
Fallopian tube sperm perfusion
Factors affecting outcome of IVF
• Salpingectomy before IVF for women with
hydrosalpinges
• Optimal age 23-39 years
• Increased success with previous pregnancy
and/or live birth
• Ideal Body Mass Index is 19-30
• Increased success with low alcohol/caffeine
intake
• Increased success in non-smokers
• Consistent outcome for first 3 cycles of
treatment, effectiveness after 3 cycles is
uncertain
IVF
• If no pregnancy with oligozoospermia,
bilateral tubal occlusion or 3 years’ infertility
and the woman is aged 23-39 years:
offer up to 3 cycles of IVF
• Additional principles of care:
– Access to evidence-based information (verbal and
written) on risks/implications of assisted
conception, including health of resulting children;
genetic counselling; consideration of welfare of the
child
Procedures in IVF treatment - 1
• Offer screening
- HIV, hepatitis B, C, specialist referral if positive
• Ovulatory stimulation
- No natural cycle
- GnRH agonist down regulation or
agonist with gonadotrophins to reduce cost
- No antagonists, no Growth hormone
- Monitor follicular development with
ultrasound: have a protocol to manage OHSS
- Oocyte maturation with hCG
- Oocyte retrieval: offer conscious sedation
- No follicle flushing, no assisted hatching
Procedures in IVF treatment - 2
• Embryo transfer
- Not >2 transferred in any one cycle
- Offer cryostorage if >2 embryos
- Frozen embryos to be transferred before further
stimulated cycle
- Ultrasound guided embryo transfer on
day 2 or 3, or day 5 or 6
• Luteal support
- progesterone
Management options with IVF
or other forms of ART - 1
• ICSI
- Severe semen defects, azoospermia
- Poor IVF treatment response
- Screen by karyotype
• Donor insemination
- Azoospermia
- Genetic disease in male partner
- Severe rhesus isoimmunisation
- Severe semen defects
For female:
- Confirm ovulation, HSG if no pregnancy after 3 cycles
Management options with IVF or
other forms of ART - 2
• Oocyte donation
- Premature ovarian failure
- Gonadal dysgenesis including Turner syndrome
- Bilateral oophorectomy
- Ovarian failure following chemo- or radio-therapy
- Some cases of IVF treatment failure
- Gene disorder transmission to offspring
- Screen donors
- Risks of ovarian stimulation and egg collection
• Egg sharing - counselling
Key priorities in infertility management (3/6)
before IVF
Assessing tubal occlusion
and uterine abnormalities
• Screen for Chlamydia before uterine instrumentation B
(A key priority)
• If positive, treat and refer the sexual partner for screening C
• Consider prophylactic antibiotics before uterine
instrumentation if not screened GPP
• If no co-morbidities (pelvic inflammatory disease, previous ectopic,
endometriosis) offer HSG (hysterosalpingogram [or hysterosalpingocontrast-sonography] A) to screen for tubal occlusion B (A key
priority)
• If co-morbidities, offer laparoscopy B
• Hysteroscopy should be clinically indicated and not used routinely.
Treatment of uterine anomalies is not clearly linked to fertility B
• Do not use routine post-coital testing of cervical mucus as it has no
predictive value for pregnancy rate A
Intrauterine insemination
• Mild male factor, unexplained infertility and
mild to moderate endometriosis should
have 6 cycles of IUI A (A key priority)
• It should be unstimulated IUI in male factor
and unexplained infertility A
• Use stimulated IUI for mild to moderate
endometriosis A
• Use single insemination (A) and Fallopian
tube perfusion A
Standards of Care (BFS/RCOG)
STANDARD
Primary Care
Organisation of services
Initial investigation
CORE
Local protocols
Progesterone, Rubella,
Chlamydia
& Semen Analysis
ASPIRATIONAL
Dedicated staff
Same laboratory
for Semen Analysis
Secondary Care
Location of Services
Availability of service
Access to
infertility clinics
Patient information
Written information leaflets
Consultation room
Competence of clinical &
nursing staff
Where appropriate
staff & facilities
5 day & Weekend cover
Standard
Network
24/7 access to information
Direct referral
from General
Practitioner
Verbal & written in
languages
With contact details
Private
Online also
Dedicated
Trained
Multidisciplinary meeting
Clear
See Consultant at
alternate visits
BFS/RCOG Standards of Care
Summary
And so on… through secondary and tertiary care; also providing auditable standards
for the Clinic, the Andrology lab and the Assisted Reproduction clinic
Secondary Care
• Initial investigations
• Pelvic assessment
• Patient choice of management
• Support services
• Ovulation induction
• Unexplained infertility
• Endometriosis
Tertiary Care
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Location of Services
Organisational and
management responsibility
Quality management
Resource management
Assisted conception services
Gamete donation
Evaluation and improvement
Continuing professional
development
CONCLUSION
• A great deal of preparation is required
before IVF can be implemented:
- agreed protocols
- informed staff
- patients prepared factually and
emotionally
- Efficient, responsible organisation