This document discusses guidelines for assessing and treating fertility problems from 2013. It covers: - Common causes of fertility issues including unexplained infertility and male/female factors - Terms used in fertility treatment like infertility and full IVF cycle - Recommendations for treatments like not offering oral drugs for unexplained infertility and IUI, and criteria for IVF referral - Principles of care like providing information to couples and counseling on chances of conception - Investigations for fertility problems and how to interpret results - Medical and surgical treatment options for issues like ovulation disorders, tubal problems, endometriosis, and male factor infertility - Procedures used in IVF treatment including controlled ovarian stimulation protocols

1. Assessment and treatment of
people with fertility problem
NICE guideline, 2013
Aboubakr Elnashar
Benha university, Egypt
Aboubakr Elnashar

2. 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.
Aboubakr Elnashar

3. 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
Aboubakr Elnashar

4. 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
Aboubakr Elnashar

5. 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
Aboubakr Elnashar

6.  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
Aboubakr Elnashar

7. 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.
Aboubakr Elnashar

8. 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.
Aboubakr Elnashar

9.  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
Aboubakr Elnashar

10. Principles of care
Aboubakr Elnashar

11. 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.
Aboubakr Elnashar

12. 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.
Aboubakr Elnashar

13. 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
Aboubakr Elnashar

14. 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
Aboubakr Elnashar

15. BMI: Females:
>30: longer to conceive.
>30 who are not ovulating: losing weight increase
chance of conception
Men
>30: reduced fertility,
Aboubakr Elnashar

16. <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.
Aboubakr Elnashar

17. 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.
Aboubakr Elnashar

18. Investigation of fertility problems and
management strategies
Aboubakr Elnashar

19. 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.
Aboubakr Elnashar

20. Semen analysis: WHO, 2010
:
:
Lower reference limitParameter
1.5 mlVolume
7.2pH
15 million/mlConcentration
39 million/ejaculateTotal sperm number
40% or
PR: 32%
Total motility: (PR+NP)
58% live spermatozoaVitality
4% (strict criteria).Normal forms
Aboubakr Elnashar

21. 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
Aboubakr Elnashar

22. 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}
Aboubakr Elnashar

23. 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
Aboubakr Elnashar

24. High
response
Low
response
164Total AFC
40.5AMH ng/ml
48.9FSH IU/L
Aboubakr Elnashar

25.  Do not use
1. ovarian volume
2. ovarian blood flow
3. inhibin B
4. oestradiol (E2)
Aboubakr Elnashar

26. 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
Aboubakr Elnashar

27. 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
Aboubakr Elnashar

28. 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]
Aboubakr Elnashar

29. Medical and surgical management of
male factor fertility problems
Aboubakr Elnashar

30. 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]
Aboubakr Elnashar

31.  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}
Aboubakr Elnashar

32. Ovulation disorders
Aboubakr Elnashar

33. WHO classification
 Group I: hypothalamic pituitary failure
(hypothalamic amenorrhoea or
hypogonadotrophic hypogonadism).
 Group II: hypothalamic-pituitary-ovarian
dysfunction (predominately pcos).
 Group III: ovarian failure.
Aboubakr Elnashar

34. 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.
Aboubakr Elnashar

35. 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.
Aboubakr Elnashar

36. 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
Aboubakr Elnashar

37. 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.
Aboubakr Elnashar

38. Hyperprolactinaemic amenorrhoea
 dopamine agonists such as bromocriptine.
Aboubakr Elnashar

39. Monitoring ovulation induction during
gonadotrophin therapy
 Ovarian ultrasound monitoring:
measure follicular size and number
{reduce the risk of multiple pregnancy and
ovarian hyperstimulation}.
Aboubakr Elnashar

40. Tubal and uterine
surgery
Aboubakr Elnashar

41. 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}.
Aboubakr Elnashar

42. o proximal tubal obstruction
selective salpingography plus tubal
catheterisation, or
hysteroscopic tubal cannulation, may be
treatment options {improve the chance of
pregnancy]
Aboubakr Elnashar

43.  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]
Aboubakr Elnashar

44. Medical and surgical
management of endometriosis
Aboubakr Elnashar

45.  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]
Aboubakr Elnashar

46.  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.
Aboubakr Elnashar

47. 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.
Aboubakr Elnashar

48. 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.
Aboubakr Elnashar

49. Procedures used during IVF
treatment
Aboubakr Elnashar

50. 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.
Aboubakr Elnashar

51. 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.
Aboubakr Elnashar

52. 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
Aboubakr Elnashar

53.  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.
Aboubakr Elnashar

54. Triggering ovulation in IVF
 HCG (urinary or recombinant) to trigger
ovulation in IVF treatment.
 protocols for preventing, diagnosing and
managing OHSS.
Aboubakr Elnashar

55. 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.
Aboubakr Elnashar

56.  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

57. 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

58. 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

59. Thanks
Aboubakr Elnashar