Assessment and treatment of people with fertility problemNICE guideline, 2013
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Assessment and treatment of
people with fertility problem NICE guideline, 2013
Aboubakr Elnashar
Benha university, Egypt
Aboubakr Elnashar
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Fertility incidence
1 in 7 couples
Main causes: unexplained infertility: 25% ovulatory disorders: 25% tubal damage: 20% male factors: 30% uterine or peritoneal: 10% combined male and female: 40% Uterine or endometrial factors, gamete or embryo
defects, and pelvic conditions such as endometriosis may also play a role.
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Terms
Full cycle:
one episode of ovarian stimulation and transfer
of any resultant embryos fresh or frozen.
Infertility:
reproductive age woman
one year unprotected sexual intercourse
absence of known cause of infertility
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Unexplained infertility
Do not offer oral ovarian stimulation agents (such as clomifene citrate, or letrozole).
{no increase the chances of a pregnancy or a live birth}.
Offer IVF after 2 years
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Intrauterine insemination
unexplained infertility
mild endometriosis or
‘mild male factor:
Do not routinely offer IUI, either with or without ovarian stimulation
Advise: try to conceive for a total of 2 years (include 1 year before their fertility investigations) then IVF
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Unstimulated IUI indication:
1. unable to, or would find it very difficult to, have vaginal intercourse
{physical disability or
psychosexual problem} .
If not conceived after 6 ovulatory cycles, offer a further 6 cycles of unstimulated IUI before IVF is considered
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Criteria for referral for IVF
under 40 ys:
not conceived after
2 years of regular unprotected intercourse or
6 cycles of IUI: 3 full cycles of IVF.
40–42 years:
offer 1 full cycle of IVF, provided the following 3 criteria are fulfilled:
never previously had IVF treatment
no evidence of low ovarian reserve
discussion of the additional implications of IVF and pregnancy at this age.
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Number of fresh or frozen embryo transfer
<37 years:
First full IVF cycle:
single embryo transfer.
Second full IVF cycle:
single embryo transfer if 1 or more top-quality embryos are available.
Consider using 2 embryos if no top-quality embryos are available.
Third full IVF cycle:
transfer no more than 2 embryos.
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37–39 years:
First and second full IVF cycles:
Single embryo transfer if there are 1 or more top-quality embryos.
Consider double embryo transfer if there are no top-quality embryos.
Third full IVF cycle:
transfer no more than 2 embryos.
40–42 years
double embryo transfer.
So: SET except
1. After 40
2. 3rd cycle
3. 2nd cycle if no goood quality E
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Principles of care
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Providing information
See the couples together.
Verbal information should be supplemented with written information or audio-visual media
Frequent counseling after every investigation and step.
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Chance of conception counseling
Psychological effects of infertility: reduced lipido and coital frequency.
sexual intercourse every 2 to 3 days optimises the chance of pregnancy.
>80% <40yrs with regular intercourse will conceive within 1 year
90% in two yrs.
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Smoking
Reduce female fertility
Passive smoking is likely to affect their chance of
conceiving
An association between smoking and reduced
semen quality (although the impact of this on male
fertility is uncertain), and that stopping smoking will
improve their general health
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Caffeinated beverages
No association between coffee, tee or colas
with fertility.
Maternal caffeine consumption has adverse
effects on the success rates of ART.
also alcohol and smoking
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BMI: Females:
>30: longer to conceive.
>30 who are not ovulating: losing weight increase
chance of conception
Men
>30: reduced fertility,
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<19
irregular menstruation or are not menstruating
increasing body weight improve chance of conception.
Tight underwear
: elevated scrotal temperature and reduced semen
quality,
loose-fitting underwear
improves fertility: uncertain.
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Folic acid supplementation
before conception and up to 12 w reduces the risk of NTD.
Dose: 0.4 mg per day.
5 mg per day
previous NTD
anti-epileptics
diabetics.
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Investigation of fertility problems and
management strategies
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Semen analysis
vol: 1.5 ml or more
pH: 7.2 or more
Concentration: 15 million spermatozoa/ ml or more
total sperm number: 39 million spermatozoa per ejaculate or more
total motility: (PR+NP): 40% or more or
PR: 32% or more
vitality: 58% or more live spermatozoa
Normal forms: 4% or more.
based on strict morphological criteria.
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Semen analysis: WHO, 2010
:
:
Lower reference limit Parameter
1.5 ml Volume
7.2 pH
15 million/ml Concentration
39 million/ejaculate Total sperm number
40% or PR: 32%
Total motility: (PR+NP)
58% live spermatozoa Vitality
4% (strict criteria). Normal forms
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Other consensus threshold values
pH ≥7.2
Peroxidase-positive leukocytes (106 per ml)
<1.0
MAR test (motile spermatozoa with bound
particles, %) <50
Immunobead test (motile spermatozoa with bound
beads, %) <50
Seminal zinc (ųmol/ejaculate) ≥2.4
Seminal fructose (ųmol/ejaculate) ≥13
Seminal neutral glucosidase (mU/ejaculate) ≥20
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o Antisperm antibodies
should not be offered
{no evidence of effective treatment}.
If first semen analysis is abnormal:
repeat 3 months later
{allow time for the cycle of spermatozoa formation to be completed}
a single-sample analysis will falsely identify about 10% of men as abnormal, but repeating the test reduces this to 2%
if a gross spermatozoa deficiency (azoospermia or severe oligozoospermia):
repeat as soon as possible
Post-coital testing:
not recommend {no predictive value on pregnancy rate}
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Ovarian reserve testing
Woman's age an initial predictor of overall chance of success
Predictors of ovarian response to gonadotrophin stimulation in IVF:
1. Total antral follicle count less than or equal to 4 for a low response >16 for a high response 2. AMH less than or equal to 5.4 pmol/l (0.8ng/ml) for a low response
and greater than or equal to 25.0 pmol/l (3.5ng/ml)for a high
response. Conevrsion ratio:7 3. FSH >8.9 IU/l for a low response and <4 IU/l for a high response
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High
response
Low
response
16 4 Total AFC
4 0.5 AMH ng/ml
4 8.9 FSH IU/L
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Do not use
1. ovarian volume
2. ovarian blood flow
3. inhibin B
4. oestradiol (E2)
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Regularity of menstrual cycles
Regular monthly menstrual cycles: likely to be ovulating
Measure serum progesterone in the mid-luteal phase of their cycle (day 21 of a 28-day cycle) to confirm ovulation even if they have regular menstrual cycles
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Investigations 1. Midluteal progesterone
in regular and irregular cycles
{confirm ovulation} In irregular prolonged cycles
Depending upon the timing of menstrual periods, conducted later in the cycle (for example day 28 of a 35-day cycle) and repeated weekly thereafter until the next menstrual cycle starts
2. Basal FSH and LH
Only in
irregular prolonged cycles
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3. Prolactin
Only in
ovulatory disorder
galactorrhoea or
pituitary tumour
4. TSH:
only if
symptoms of thyroid disease
Endometrial biopsy
To evaluate the luteal phase: No
{no evidence that medical tt of luteal phase defect improves pregnancy rates]
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Medical and surgical management of
male factor fertility problems
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male factor infertility
hypogonadotrophic hypogonadism: gonadotrophin drugs {effective}
idiopathic semen abnormalities:
No anti-oestrogens, gonadotrophins, androgens, or bromocriptine {not effective]
leucocytes in semen:
No antibiotic treatment unless there is an identified infection {no evidence that this improves pregnancy rates]
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Obstructive azoospermia:
surgical correction of epididymal blockage, IF EXPERIENCE [likely to restore patency of the duct and improve fertility}.
Varicoceles
No varicocelectomy.
{does not improve pregnancy rates}
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Ovulation disorders
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WHO classification
Group I: hypothalamic pituitary failure (hypothalamic amenorrhoea or hypogonadotrophic hypogonadism).
Group II: hypothalamic-pituitary-ovarian dysfunction (predominately pcos).
Group III: ovarian failure.
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WHO Group I
increasing body weight if they have a BMI <19
Moderating exercise levels if they undertake high levels of exercise.
pulsatile administration of gonadotrophin-releasing hormone or
gonadotrophins with LH activity to induce ovulation.
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WHO Group II
BMI of 30 or over: lose weight.
{alone may restore ovulation, improve their response to ovulation induction agents, and have a positive impact on pregnancy outcomes]
Then one of the following treatments, taking into account potential adverse effects, ease and mode of use, the woman's BMI, and monitoring needed:
clomifene citrate or
metformin or a
combination.
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o clomifene citrate:
ultrasound monitoring during at least the first cycle of treatment to ensure that they are taking a dose that minimises the risk of multiple pregnancy.
Do not continue for longer than 6 months.
o Metformin
side effects: nausea, vomiting and other gastrointestinal disturbances
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Resistant to clomifene citrate:
consider one of the following second-line
treatments, depending on clinical
circumstances and the woman's preference:
1. laparoscopic ovarian drilling or
2. combined treatment with clomifene citrate
and metformin if not already offered as first-
line treatment or
3. gonadotrophins.
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Hyperprolactinaemic amenorrhoea
dopamine agonists such as bromocriptine.
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Monitoring ovulation induction during
gonadotrophin therapy
Ovarian ultrasound monitoring:
measure follicular size and number
{reduce the risk of multiple pregnancy and
ovarian hyperstimulation}.
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Tubal and uterine surgery
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o mild tubal disease:
tubal surgery (Tubal microsurgery and laparoscopic tubal surgery)
may be more effective than no treatment.
In centres where appropriate expertise is available it may be considered as a treatment option.
Hydrosalpinges
salpingectomy, preferably by laparoscopy, before IVF treatment {improves the chance of a live birth}.
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o proximal tubal obstruction
selective salpingography plus tubal catheterisation, or
hysteroscopic tubal cannulation, may be treatment options {improve the chance of pregnancy]
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Uterine surgery
Women with amenorrhoea who are found to have intrauterine adhesions should be offered hysteroscopic adhesiolysis [restore menstruation and improve the chance of pregnancy]
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Medical and surgical management of endometriosis
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Medical management (ovarian suppression) of endometriosis
Does not enhance fertility and should not be offered.
Surgical ablation
minimal or mild endometriosis who undergo laparoscopy should be offered surgical ablation or resection of endometriosis plus laparoscopic adhesiolysis {improves the chance of pregnancy]
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ovarian endometriomas
laparoscopic cystectomy {improves the chance of pregnancy}
Moderate or severe endometriosis
surgical treatment {improves the chance of pregnancy]
Post-operative medical treatment does not improve pregnancy and is not recommended.
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Prediction of IVF success
1. Female age
Success falls with rising female age
2. Number of previous treatment cycles
Chance of a live birth following IVF treatment falls as the number of unsuccessful cycles increases.
3. Previous pregnancy history
IVF treatment is more effective in women who have previously been pregnant.
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4. BMI
should ideally be in the range 19–30 before commencing assisted reproduction, and that a female BMI outside this range is likely to reduce the success of assisted reproduction procedures.
5. Lifestyle factors
i. more than 1 unit of alcohol per day
ii. maternal and paternal smoking, and
iii. maternal caffeine consumption can adversely affect IVF success rates.
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Procedures used during IVF treatment
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Pre-treatment in IVF
oral contraceptive pill or a progestogen:
does not affect the chances of having a live birth.
Consider pre-treatment in order to schedule IVF
treatment for women who are not undergoing long
down-regulation protocols.
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Down regulation and other regimens to avoid
premature luteinising hormone surges in IVF
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.
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Controlled ovarian stimulation in IVF
Use either urinary or recombinant gonadotrophins for ovarian stimulation as part of IVF treatment.
use an individualised starting dose of follicle-stimulating hormone, based on factors that predict success, such as:
1. age
2. BMI
3. presence of polycystic ovaries
4. ovarian reserve
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do not use a dosage of FSH of more than 450 IU/day.
Do not offer women 'natural cycle' IVF treatment.
Do not use
growth hormone or
dehydroepiandrosterone (DHEA) as adjuvant treatment in IVF protocols.
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Triggering ovulation in IVF
HCG (urinary or recombinant) to trigger ovulation in IVF treatment.
protocols for preventing, diagnosing and managing OHSS.
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Oocyte retrieval in IVF
Follicle flushing
does not increase the numbers of oocytes retrieved
or pregnancy rates, and increases the duration of
oocyte retrieval and associated pain.
Assisted hatching
not recommended because it has not been shown
to improve pregnancy rates.
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Embryo transfer strategies in IVF
Ultrasound-guided
improves pregnancy rates.
Endometrium thickness
less than 5 mm unlikely to result in a pregnancy and is therefore not recommended.
Bed rest
more than 20 minutes' duration following embryo transfer does not improve the outcome of IVF treatment.
Embryo quality evaluation
at both cleavage and blastocyst stages,
The likelihood of a live birth after replacement of frozen–thawed embryos is similar for embryos replaced during natural cycles and hormone-supplemented cycles.
Aboubakr Elnashar
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Luteal phase support after IVF
Progesterone for luteal phase support after IVF
treatment.
No HCG for luteal phase support after IVF treatment
[increased likelihood of ovarian hyperstimulation
syndrome]
The evidence does not support continuing any form of
treatment for luteal phase support beyond 8 weeks'
gestation.
Aboubakr Elnashar
![Page 58: Assessment and treatment of people with fertility problemNICE guideline, 2013](https://reader034.fdocuments.in/reader034/viewer/2022051609/547e5d335806b5c75e8b468c/html5/thumbnails/58.jpg)
Intracytoplasmic sperm injection
Indications for ICSI:
1. severe deficits in sperm quality
2. Azospermia
3. previous IVF treatment cycle resulted in failed or very poor fertilisation.
ICSI versus IVF
Improves fertilisation rates,
but once fertilisation is achieved the pregnancy rate is no better than with IVF.
Aboubakr Elnashar
![Page 59: Assessment and treatment of people with fertility problemNICE guideline, 2013](https://reader034.fdocuments.in/reader034/viewer/2022051609/547e5d335806b5c75e8b468c/html5/thumbnails/59.jpg)
Thanks
Aboubakr Elnashar