MANAGEMENT OF INFERTILITY CURRENT GUIDELINES

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MANAGEMENT OF INFERTILITYCURRENT GUIDELINES

• DR NOSHABA RAFIQ
• M.B.B.S. M.C.P.S. F.C.P.S.

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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

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BACKGROUND INFORMATION

• At puberty there are 300,000 primordial follicles
• Dominant follicle produces oestradiol which leads
  to LH surge
• Ovulation occurs 24-36 hours later
• The fertilization life span of the ovum is 24-36
  hours
• The receptivity of the endometrium is days 16-19
  of a 28 day cycle

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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 12-24 months of trying

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BACKGROUND INFORMATION

• The single most important determinant of a
  couples 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

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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

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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)

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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 .

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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

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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

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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

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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.

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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 .

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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 .

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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

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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

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DIAGNOSIS OF PCOS

• Ultrasound is the gold standard for the diagnosis
  of PCO.
• The diagnostic criteria is of 10 discrete
  follicles of lt10mm usually peripherally arranged
  around an enlarged, hyperechogenic central stoma

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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

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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

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Tests which are not consistently correlated with
pregnancy

• Zona free hamster egg penetration tests
• Post-coital test
• Antisperm antibodies assays

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Tests which seem NOT to correlate with pregnancy

• Endometrial dating
• Varicocoel assessment
• Chlamydial testing
• MAY HAVE A ROLE IN SPECIAL SITUATIONS

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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.

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MANAGEMENT

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

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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.

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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

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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, womens fertility as well
  as semen quality
• Excessive alcohol is detrimental to semen quality
  and may cause erectile dysfunction

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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

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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
  womans 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 .

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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 .

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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.

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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.

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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.

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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.

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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

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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

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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 .

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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 .

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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 .

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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

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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 .

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OVULATION DISORDERS

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

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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.

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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.

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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 .

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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.

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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.

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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 .

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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

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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.

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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.

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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
  couples with unexplained infertility

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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

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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

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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

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P0INT TO REMENBER

• ONE SATISFIED PATIENT IS WORTH THOUSANDS OF
  GUIDELINES AND PROTOCALS

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THANK YOU