1. MANAGEMENT OF INFERTILITY CURRENT GUIDELINES

2. OBJECTIVES
To present the recent concepts in the management of infertility
To draw clinically relevant conclusions based on:
META-ANALYSIS
RANDOMISED CONTROLLED TRIALS
GUIDELINES AND PROTOCOLS
To discuss the best possible clinical management options with local perspective

3. BACKGROUND INFORMATION
At puberty there are 300,000 primordial follicles
Dominant follicle produces oestradiol which leads to LH surge
Ovulation occurs hours later
The fertilization life span of the ovum is hours
The receptivity of the endometrium is days of a 28 day cycle

4. BACKGROUND INFORMATION
Infertility is rarely absolute so the term sub-fertility may be more appropriate
About 84% of couples would conceive within one year of trying for a pregnancy
Another 8% would conceive in the next year giving a cumulative pregnancy rate of 92% at the end of two years
Subfertility is defined as the inability to conceive within months of trying

5. BACKGROUND INFORMATION
The single most important determinant of a couple’s fertility is the age of the female partner:
At the age of up to 25 years CCR is 60% at six months and 85% at one year
At the age of 35 years or more the CCR is 60% at one year and 85% at two years

6. BACKGROUND INFORMATION
The other factors influencing the likelihood of a spontaneous pregnancy are:
Duration of subfertility
Occurrence of a previous pregnancy
The effect of age on male fertility, however is less clear
Any change in the prevalence of subfertility in recent years is a difficult question to answer but the male fertility is declining

7. CURRENT GUIDELINES
The current clinical approach to the investigations and the management of infertility is backed by the evidence-based guidelines issued by:
Royal College of Obstetricians and Gynaecologists (RCOG)
American Society of Reproductive Medicine (ASRM)
European Society of Human Reproduction and Embryology (ESHRE)

8. INVESTIGATIONS
The male partner should normally have two semen analyses performed during the initial investigation.
Laboratories that perform semen analysis should undertake this according to recognised WHO methodology.
Laboratories should also practice internal quality control and belong to an external quality control scheme .

9. INVESTIGATIONS
While regular menstruation is strongly suggestive of ovulation, this should be confirmed by the measurement of serum progesterone in the mid-luteal phase
There is no value in measuring thyroid function or prolactin in women with a regular menstrual cycle, in the absence of galactorrhoea or symptoms of thyroid disease

10. INVESTIGATIONS
Early follicular phase estimation of FSH and LH is only performed if clinically indicated
The female partner should normally have a test of tubal patency during the initial investigation of infertility

11. INVESTIGATIONS
A hysterosalpingogram may be used as a screening test for tubal patency in low risk couples
When an evaluation of the pelvis is required, however, a diagnostic laparoscopy with dye transit is the procedure of choice

12. INVESTIGATIONS
Ultrasound scan and hydrotubation has not been widely adopted.
The images obtained by falloposcopy are not yet of sufficiently good quality to provide useful clinical information.

13. INVESTIGATIONS
Before any uterine instrumentation, consideration should be given either to screening women for Chlamydia trachomatis, using an appropriately sensitive technique, or using appropriate antibiotic prophylaxis .

14. INVESTIGATIONS
Endometrial biopsy to evaluate the luteal phase should not be performed as part of the routine investigation of the infertile couple
The postcoital test is not recommended in the routine investigation of the infertile couple
Sperm function tests are specialised tests and should not be used in the routine investigation of the infertile couple .

15. INVESTIGATIONS
Routine testing for antisperm antibodies in semen is not recommended
Hysteroscopy should not be considered as a routine investigation in the infertile couple as there is no evidence linking the treatment of uterine abnormalities with enhanced fertility
An ultrasound examination of the endometrium is unnecessary in the initial investigation of infertility. However, ultrasound evaluation of the ovaries may be useful

16. DIAGNOSIS OF PCOS
The debate was resolved in Rotterdam in May 2003 At PCOS consensus workshop
It was agreed that two of the following three criteria were essential to establish diagnosis:
OVARIAN DYSFUNCTION
CLINICAL OR BIOCHEMICAL EVIDENCE OF HYPERANDROGENISM
POLYCYSTIC OVARIAN MORPHOLOGY ON ULTRASOUND

17. DIAGNOSIS OF PCOS
Ultrasound is the gold standard for the diagnosis of PCO.
The diagnostic criteria is of 10 discrete follicles of <10mm usually peripherally arranged around an enlarged, hyperechogenic central stoma

18. WHICH INVESTIGATIONS?
Diagnostic tests for infertility were classified into following three categories by ESHRE Capri workshop in 2000
Tests which have an established correlation with pregnancy
Tests which are not consistently correlated with pregnancy
Tests which seem NOT to correlate with pregnancy

19. Tests which have an established correlation with pregnancy
Semen analysis
Tubal patency test by HSG or Laparoscopy
Mid luteal serum progesterone for the diagnosis of ovulation

20. Tests which are not consistently correlated with pregnancy
Zona free hamster egg penetration tests
Post-coital test
Antisperm antibodies assays

21. Tests which seem NOT to correlate with pregnancy
Endometrial dating
Varicocoel assessment
Chlamydial testing
MAY HAVE A ROLE IN SPECIAL SITUATIONS

22. MANAGEMENT
The management of infertility should take place in a dedicated infertility clinic staffed by an appropriately trained professional team with facilities for investigating and managing problems in both partners.

23. MANAGEMENT Both partners should be seen together
Privacy and sufficient clinical time
Classical history taking with emphasis on exploring a couple’s anxieties
Counseling is very important and essential
Routine examination is not necessary unless indicated by the history

24. MANAGEMENT
Each stage in the investigation and treatment of infertility should be fully explained to the couple.
Written information in a range of languages should be available where appropriate.
Environmental factors can affect fertility and therefore an occupational history should be taken.

25. MANAGEMENT
The management of the individual couple should always be discussed in the context of their particular clinical situation.
Patients should be fully involved in decisions regarding their treatment.
Couples should also have access to infertility counselors outside the clinical team, and to patient support groups

26. GENERAL ADVICE TO THE COUPLE
Sexual intercourse every 2-3 days
Timed intercourse to coincide with ovulation causes stress and not to be recommended
Smoking reduces both, women’s fertility as well as semen quality
Excessive alcohol is detrimental to semen quality and may cause erectile dysfunction

27. GENERAL ADVICE TO THE COUPLE
A body mass index of more than 29 is associated with reduced fertility in both men and women
Folic acid supplement prior to conception and up to 12 weeks of conception
Rubella immunity should be checked
If vaccinated then advise to avoid pregnancy for at least one month after vaccination

28. MALE INFERTILITY
In considering the results of semen analysis for the individual couple, it is important to take into account the duration of infertility, the woman’s age and the previous pregnancy history .
Further investigations of the male partner should be preceded by a clinical examination including an assessment of secondary sexual characteristics and testicular size .

29. MALE INFERTILITY
Further investigations of the male partner may include endocrine tests, microbiological assessment of the semen and imaging of the genital tract but should be initiated in the context of a specialist infertility clinic.
Laboratories reporting semen analysis results should establish normal ranges for their own populations and indicate these on report sheets .

30. MALE INFERTILITY
Certain in vitro tests of sperm function can be of use in predicting fertility . However, at this stage, their use and interpretation should be restricted to those few centres with relevant expertise.
Surgery on the male genital tract should be carried out only in centres where there are appropriate facilities and trained staff.

31. MALE INFERTILITY
Testicular biopsy should be performed only in the context of a tertiary service where there are facilities for sperm recovery and cryostorage.
Vasectomy reversal is an effective treatment for men who want to reverse their sterilisation.
Surgical correction of epididymal blockage can be considered in cases of obstructive azoospermia.
Where a diagnosis of hypogonadotrophic hypogonadism is made in the male partner the use of gonadotrophin drugs is an effective fertility treatment.

32. MALE INFERTILITY
Bromocriptine is an effective treatment for sexual dysfunction in men with hyperprolactinaemia.
Intrauterine insemination is an effective treatment where the man has mild abnormalities of semen quality.
Infection of the male genital tract should be treated if present, but there is no evidence that this will improve fertility.

33. MALE INFERTILITY
Anti-oestrogens, androgens, bromocriptine and kinin-enhancing drugs have not been shown to be effective in the treatment of Male infertility
Antioxidants, mast cell blockers and alpha blockers need further evaluation.
The use of systemic corticosteroids for treatment of antisperm antibodies can only be recommended in the context of further research.

34. MALE INFERTILITY
There is no evidence that semen quality and pregnancy rates improves in men with normal sperm count after surgical treatment of a clinically apparent varicocele
The benefits of the treatment of a varicocele in oligozoospermic men is less certain

35. MALE INFERTILITY
IVF and ICSI are effective treatments for men with moderate to severe semen abnormalities
ICSI has made it possible for men with only few sperms to become fathers
Sperms for ICSI can be obtained by TSA are directly from testicular biopsy as well as aspiration from epididymus

36. TUBAL INFERTILITY
Tubal surgery should be carried out only in centres where there are appropriate facilities and trained staff.
Where proximal tubal obstruction is suspected this should be confirmed by selective salpingography and a tubal catheterisation procedure may be attempted.
Tubal surgery may be appropriate for selected cases of mild distal tubal disease or proximal tubal obstruction.
If pregnancy has not occurred within 12 months of tubal surgery, IVF should be discussed .

37. TUBAL INFERTILITY
When distal tubal surgery is performed, a microsurgical approach using magnification should be used.
A laparoscopic approach can be used for adhesiolysis but the use of this approach for salpingostomy needs more evaluation .
IVF should be considered as the first line treatment for moderate to severe distal tubal disease .

38. TUBAL INFERTILITY
The presence of hydrosalpinges is associated with reduced pregnancy rates following IVF.
Tubal reanastomosis is an effective treatment for women who want to reverse their sterilisation.
High success rates can be achieved when reversing mechanical tubal occlusion using a microsurgical approach .

39. TUBAL INFERTILITY
IVF should be considered first line treatment for moderate to severe tubal disease
Both surgery and IVF should be discussed without bias
There is no randomised comparison between IVF and tubal surgery

40. OVULATION DISORDERS
Before ovulation induction is considered, further investigations will be necessary and these should be carried out only in a specialist clinic .
In undertaking ovulation induction, centres should adopt protocols which minimise the risk of multiple pregnancy and ovarian hyperstimulation .

41. OVULATION DISORDERS
Patients undergoing ovulation induction must be given information about the risks of multiple pregnancy, ovarian hyperstimulation and the possibility of fetal reduction.

42. OVULATION DISORDERS
Clomiphene is an effective treatment for anovulation in appropriately selected women
Cumulative Pregnancy Rate continues to rise until ten cycles of treatment. RCOG recommends that up to 12 cycles of treatment should be considered
Ovulation induction with clomiphene should only be performed in circumstances which allow access to ovarian ultrasound monitoring.

43. OVULATION DISORDERS
With clomiphene ovulation occurs in 70-80% and the cumulative rate over six months is 60%
Seventy percent achieve pregnancy at doses of 100 mgs or less
Most evidence point towards less pregnancy rate above 100 mgs.

44. OVULATION DISORDERS
FSH and hMG are both effective for ovulation induction in women With clomiphene-resistant polycystic ovarian syndrome (PCOS).
There is no advantage in routinely using gonadotrophin-releasing hormone analogues in conjunction with gonadotrophins for ovulation induction in women with clomiphene-resistant PCOS. Furthermore, their use may be associated with an increased risk of ovarian hyperstimulation .

45. OVULATION DISORDERS
Laparoscopic ovarian drilling with either diathermy or laser is an effective treatment for anovulation in women with clomiphene-resistant PCOS. However, more research is needed into the sequelae of causing ovarian damage in this way.
The pulsatile administration of gonadotrophin-releasing hormone is an effective treatment for women with anovulation due to hypothalamic factors.

46. OVULATION DISORDERS
Dopamine agonists are effective treatment for women with anovulation due to hyperprolactinaemia
Ovulation induction with gonadotrophins should only be performed in circumstances which permit daily monitoring of ovarian response .
The criteria for abandoning ovulation induction cycles must be carefully defined in each specialist centre.

47. OVULATION DISORDERS
The association between ovarian cancer risk and gonadotrophins or prolonged clomiphene use remains uncertain.
There is no evidence to suggest an increased risk of ovarian cancer when clomiphene is used for less than 12 cycles.
Patients should be counseled about the putative risks of ovarian cancer associated with ovulation induction therapy. Practitioners should confine the use of gonadotrophins to the lowest effective dose and duration of use .

48. ENDOMETRIOSIS ASSOCIATED INFERTILITY
Endometriosis should be classified using the revised AFS system of classification, until such time as a proven functional classification is approved .
Surgical ablation of minimal and mild endometriosis improves fertility in subfertile women.
Medical treatment of minimal and mild endometriosis does not enhance fertility in subfertile women

49. ENDOMETRIOSIS ASSOCIATED INFERTILITY
Ovarian stimulation with intrauterine insemination is more effective than either no treatment or lUl alone in subfertile women with minimal or mild endometriosis.
There is no evidence that medical treatment of moderate and severe endometriosis either alone or as an adjunct to surgery improves fertility.
Surgical treatment of moderate and severe endometriosis may improve fertility but controlled studies and comparisons with assisted reproduction techniques are required.

50. ENDOMETRIOSIS ASSOCIATED INFERTILITY
In cases of moderate and severe endometriosis, assisted reproduction techniques should be considered as an alternative to, or following unsuccessful surgery.
Where large ovarian endometriotic cysts are detected, consideration should be given to their surgical treatment because this may enhance spontaneous pregnancy rates and improve access if IVF is considered.

51. UNEXPLAINED INFERTILITY
Unexplained infertility is a diagnosis of exclusion
Spontaneous pregnancy rate are high in first three years of trying
Clomiphene encourages multifollicular ovulation and increases the chances of pregnancy in couple’s with unexplained infertility

52. UNEXPLAINED INFERTILITY
Ovarian stimulation with intrauterine insemination is an effective treatment for couples with unexplained infertility.
GIFT is an effective treatment for couples with unexplained infertility.
IVF may be preferred because of the additional diagnostic information it provides and because it avoids laparoscopy

53. ASSISTED REPRODUCTION
These techniques have revolutionized the management of infertile couples
Entry guidelines should be followed
The women should be less than 40 years old and in good health
The couple should be aware of the emotional and financial strain

54. ASSISTED REPRODUCTION
The most common techniques used are:
Intrauterine Insemination
In-vitro fertilisation
Intracytoplasmic sperm injection
The success rate of the clinic should be told to the patient
The take home baby rate is roughly around 20%
There is no increase in the incidence of the congenital abnormalities

55. ONE SATISFIED PATIENT IS WORTH THOUSANDS OF GUIDELINES AND PROTOCALS
P0INT TO REMENBER
ONE SATISFIED PATIENT IS WORTH THOUSANDS OF GUIDELINES AND PROTOCALS

56. THANK YOU