In-Vitro Fertilisation
(NICE CG 156 - Feb 2013)

Prediction of Success

Female age: Chance of live birth falls with rising age

Number of previous treatment cycles: Overall chance falls as number of unsuccessful cycles increases

Previous pregnancy history: More effective in women who have previously been pregnancy and/or had a live birth

BMI: Ideal range 19-30

Lifestyle factors: Maternal and paternal smoking, maternal caffeine consumption, and consumption of >1 unit of alcohol/day reduces success rates of IVF

Referral Criteria

Women aged 40-42 who have not conceived after 2 years of regular UPSI or 12 cycles of artificial insemination (6 or more by IUI):

  • Offer 1 full cycle of IVF, with or without ICSI, provided 3 criteria are fulfilled:
  1. No previous IVF treatment
  2. No evidence of low ovarian reserve
  3. Discussion of implications of IVF and pregnancy at this age

Full cycle of IVF, with or without intracytoplasmic sperm injection (ICSI), should comprise 1 episode of ovarian stimulation and the transfer of any resulting fresh and frozen embryo(s)

Women aged under 40 who have not conceived after 2 years of regular UPSI or 12 cycles of artificial insemination (6 or more by IUI):

  • Offer 3 full cycles of IVF, with or without ICSI
  • If reaches age 40 during treatment, complete the cycle but do not offer further full cycles

ICSI

Procedures Used During IVF

Note that for women aged under 40, any previous full IVF cycle, whether self or NHS funded, should count towards the 3 full cycles offered by the NHS

1. Pre-treatment

2. Down-regulation and other regimens to avoid premature LH surges in IVF

Using pre-treament (either with the OCP or a progestogen) does not affect chances of having a live birth

Consider in order to schedule IVF treatment for women who are not undergoing long down-regulation protocols

Use regimens to avoid premature LH surges in gonadotrophin-stimulated IVF treatment cycles

Use either GnRH agonist down-regulation or
GnRH antagonists as part of gonadotrophin-stimulated IVF treatment cycles

Only offer GnRH agonists to women who have a
low risk of ovarian hyperstimulation syndrome

When using GnRH agonists as part of IVF treatment, use a long down-regulation protocol

3. Controlled ovarian stimulation

Use ovarian stimulation in the form of either urinary or recombinant gonadotrophins as part of IVF treatment

When using gonadotrophins for ovarian stimulation: Use an individualised starting dose of FSH, based on factors that predict success such as age, BMI, polycystic ovaries, ovarian reserve. DO NOT use a dose of FSH >450 IU/day.

Offer ultrasound monitoring (with or without oestradiol levels) for efficacy and safety throughout ovarian stimulation

DO NOT offer natural cycle IVF or use GH or DHEA as adjuvant treatment

Clomifene citrate-stimulated and gonadotrophin-stimulated
IVF cycles have higher pregnancy rates per cycle than natural cycle IVF

4. Triggering ovulation

5. Oocyte and sperm retrieval

6. Embryo transfer strategies

Offer HCG (urinary or recombinant) to trigger ovulation

Offer ultrasound monitoring of ovarian response

Protocols should be in place for managing ovarian hyperstimulation syndrome

Offer conscious sedation to women undergoing transvaginal retrieval of oocytes

Women who have developed at least 3 follicles before oocyte retrieval should NOT be offered follicle flushing as it increases duration of oocyte retrieval and pain

Surgical sperm recovery before ICSI may be performed and facilities for cryopreservation of spermatozoa should be available

Offer ultrasound guided embryo transfer as this improves pregnancy rates

Replacement of embryos with an endometrium <5mm thickness is unlikely to result in pregnancy and is NOT recommended

Bed rest of >20 minutes duration following transfer does NOT improve outcomes

Women under 37 years

  1. First full cycle: Single embryo transfer
  2. Second full cycle: Single embryo transfer if 1 or more top quality embryos available, otherwise consider using 2 embryos
  3. Third full cycle: Transfer no more than 2 embryos

Women 37-39 years

  1. First and second full cycles: Single embryo transfer if 1 or more top quality embryos, otherwise consider double embryo transfer
  2. Third full cycle: Transfer no more than 2 embryos

Women 40-42 years: Consider double embryo transfer

Evaluate embryo quality at both cleavage and blastocyst stages

For IVF with donor eggs, use an embryo transfer strategy based on the age of the donor

No more than 2 embryos should be transferred during any one cycle of IVF treatment; counsel of the risks of multiple pregnancy

Where a top-quality blastocyst is available, use single embryo transfer

Offer cryopreservation to store any remaining good-quality embryos

Advise women with regular ovulatory cycles that likelihood of a live birth after replacement of frozen-thawed embryos is similar for embryos replaced during natural cycles and hormone-supplemented cycles

7. Luteal phase support after IVF

Offer progesterone for luteal phase support up to 8 weeks

DO NOT offer HCG due to increased likelihood of ovarian hyperstimulation syndrome

Recognised indications

  1. Severe deficits in semen quality
  2. Obstructive azoospermia
  3. Non-obstructive azoospermia
  4. Consider when previous IVF treatment cycle resulted in failed or very poor fertilisation

Genetic issues and counselling

  1. Offer genetic counselling and testing if a specific genetic defect associated with male infertility is known or suspected
  2. Establish the man's karyotype if there is severe deficit of semen quality or non-obstructive azoospermia
  3. Testing for Y chromosome microdeletions: Significant proportion of male infertility results from abnormalities of genes on the Y chromosome involved in regulation of spermatogenesis

Known to improve fertilisation rates compared to IVF alone

Donor Insemination

Effective in managing infertility associated with:

  1. Obstructive azoospermia
  2. Non-obstructive azoospermia
  3. Severe deficits in semen quality in couples not wishing to undergo ICSI

Consider in conditions such as:

  1. High risk of transmitting genetic disorder to offspring
  2. High risk of transmitting infectious disease to offspring or woman from the man
  3. Severe rhesus isoimmunisation

Offer IUI in preference to intracervical insemination as it improves pregnancy rates

Oocyte Donation

Assessments for the woman

  1. Confirm that the woman is ovulating
  2. Offer tubal assessment in women with a history suggestive of tubal damage
  3. Offer tubal assessment after 3 cycles if treatment by donor insemination has been unsuccessful

Women who are ovulating regularly should be offered a minimum of 6 cycles of donor insemination without ovarian stimulation to reduce the risk of multiple pregnancy

Effective in managing infertility associated with:

  1. Premature ovarian failure
  2. Gonadal dysgenesis including Turner syndrome
  3. Bilateral oophorectomy
  4. Ovarian failure following chemotherapy or radiotherapy
  5. Certain cases of IVF treatment failure
  6. Consider where there is high risk of transmitting genetic disorders to offspring

Need to screen for infectious and genetic diseases before donation is undertaken

Cancer Patients and Fertility

Cryopreservation in males

  1. Offer sperm cryopreservation to males preparing for medical treatment for cancer likely to make them infertile
  2. Use freezing in liquid nitrogen vapour for sperm cryopreservation

Long-Term Safety of ART

IVF treatment

  1. Small increased risk of borderline ovarian tumours cannot be excluded
  2. Absolute risks of long-term adverse outcomes in children born from IVF are low
  3. Limit drugs used for controlled ovarian stimulation in IVF treatment to the lowest effective dose and duration of use

Ovulation induction and stimulation

  1. No direct association between treatments and invasive cancer
  2. No association in short-medium term between treatments and adverse outcomes including cancer in children born
  3. Limit use of ovulation induction or ovarian stimulation agents to the lowest effective dose and duration of use

Cryopreservation in females

  1. Offer oocyte or embryo cryopreservation to females preparing for medical treatment for cancer likely to make them infertile if:
  • They are well enough to undergo ovarian stimulation and egg collection
  • This will not worsen their condition
  • Enough time is available efore start of cancer treatment
  1. Uise vitrification instead of controlled rate freezing

Use sperm, embryos, or oocytes

Store cryopreserved material for an initial period of 10 years. Offer continued storage of cryopreserved sperm, beyond 10 years, to men who remain at risk of of significant infertility.