“My biological clock is running out, doctor”

Max Brinsmead MB BS PhD

April 2014

Hannah 38 and Barry 36

Have been living together for 6 years without contraception but Hannah has never conceived. She now seeks your advice because: “My biological clock is running out, doctor”

WHAT ARE THE POSSIBLE CAUSES?

Hannah & Barry Differential Diagnosis

Female FactorsAnovulationGenital tract pathology – tubes & cervix Implantation failure

Male FactorsFailure of sperm generationGenital tract pathology – epididymis, vas

and ejaculatory ductSperm delivery problems

Hannah & Barry with 6 years of infertility

Seek your advice because Hannah believes that time is running out

WHAT ADDITIONAL INFORMATION DO YOU REQUIRE?

History required of Hannah & Barry with 6 years of infertility

Previous conceptions, either partner

General health, drugs, smoking, exercise etc

Past health and any operations

Previous STDs

Menstrual history

Coital history

Hannah & Barry with 6 years of infertility

Previous conceptions?General health, drugs, smoking, exercise etcPast health and any operationsPrevious STDsMenstrual historyCoital history

Hannah TOP at age 18. Barry’s previous wife no conception in 4 yearsBarry smokes 10-15/dayBarry had a “hernia operation” in infancyHannah suffers recurrent thrush. Was treated for CIN at age 28Periods every 26-29 days. Mild dysmenorrhoeaCoitus 2-3 x per week, no problems

Hannah & Barry with 6 years of infertility

Do you examine either partner?

What tests would you request?

Any other advice?

Possible Tests for Hannah & Barry

Semen analysisHormone test for ovulationSTD screenAntenatal screen especially Rubella & VaricellaBasal body temperature chart (BBT)Gene testing for cystic fibrosis, maybeRecommend smoking cessation (Barry) and Folic acid for Hannah(Hysterosalpingogram) (Laparoscopy, hysteroscopy and dye studies)

Test Results for Hannah & Barry

Semen analysis

Routine AN tests

BBT

Volume 1 ml (NR>2) Count <1 million/ml (NR>20) Motility 30% (NR>50) Normal 0% (NR>15)

AN tests NAD but non immune to Varicella

BBT biphasic but coitus not as frequent as claimed

Hannah, 38 & Barry, 36 with 6 years of infertility have a severe male problem

What do you do now?

Examine either or both?

Repeat the semen analysis

Do more tests on Hannah?

Do more tests on Barry?

Hannah & Barry further evaluation

Examine Barry

Repeat the semen analysisBlood tests for BBlood tests for HUltrasound female pelvis

R. testis 15 ml. L testis small & soft. Epidiymis & vas deferens NADMuch the same, but volume 2 ml

FSH, Testoserone, PRL, antisperm antibodiesDay 2 FSH, LH & E2 Day 21 ProgesteroneNormal endometrium, myometrium & ovaries

Hannah, 38 & Barry, 36 with 6 years of infertility have a severe male problem

What do you do now?

Barry wants to know if there is anything that he can do about his sperm count

Is Hannah’s biological clock running out?

Hannah & Barry are advised to seek assisted conception with an IVF Clinic

What sorts of assisted conception are there?

What do they need to know?

Assisted conception options for Hannah & Barry

AIH +/- ovarian stimulationDIGIFTIVF

ICSI

Ovarian stimulation with Clomid or FSH then intrauterine insemination with washed & concentrated husband’s spermInsemination with donor spermOvarian stimulation, egg collection then fallopian tube transfer of eggs and spermOvarian stimulation, egg collection, in vitro fertilisation then uterine transfer of embryo(s).Ovarian stimulation, egg collection, sperm microinjection in vitro then uterine transfer of embryo(s).

Hannah & Barry need to understand:

What is done

What are the risks

Side effects of drugs

Pituitary suppression with GnRHa, FSH stimulation of ovaries, vaginal egg collection with ultrasound, IVF or ICSI, culture to blastocysts then uterine transfer. Extra embryos can be frozen for later attempts.1-5% risk of OHSS, 1% risk of egg collection mishap. No risk of ovarian Ca, premature menopause etc.

Few side effects of these physiological hormones used in pharmacological doses

Hannah & Barry need to understand:

Success rates

Possible cycle outcomes

Possible pregnancy outcomes

Cost

30 – 40% chance of pregnancy per embryo transfer. Depends on female age.Cycle cancellation 10%, failed egg collection 1%, failed fertilisation 5-10%

Miscarriage, ectopic (2-fold increased risk), 3% risk of chromosomal abnormality with ICSI but not IVF

Medicare eligible but most IVF programs have out of pocket costs

Endometriosis is:

Ectopic endometrium i.e. “internal menstruation”

Requires laparoscopy +/- biopsy for diagnosis

Activity is more important than appearance

Symptoms do not always correlate with grading

Symptoms of Endometriosis

The Classic Triad…

DysmenorrhoeaDyspareunia Infertility

Symptoms of Endometriosis

But consider also…

Pre menstrual stainingPain with defaecation during menstruation Intermenstrual painDisordered cyclesFamily history

Diagnosis of Endometriosis

A Careful History (The most important)

Rule out other Causes of Symptoms (The next most important)

Examination (not much help)

Ultrasound (of little value)

MRI (useful for rectovaginal deposits)

Laparoscopy (The gold standard)

Serum CA125 (Lacks sensitivity)

Iridology (a good guess!)

Differential Diagnosis:

Primary Dysmenorrhoea

Irritable Bowel Syndrome

Ovulation Pain

Pelvic Inflammatory Disease

Psychosexual Problems

Aetiology

Two Main Theories: Retrograde menstruation Peritoneal metaplasia

Predisposing Factors Familial predisposition Disordered immunity Environmental toxins Recurrent ovulation Infertile partner Obstructed menstrual flow

Principles of Management:

When the Problem is Pain – Use Medical Rx

When the Problem is Infertility – Use Surgical Rx

When there is no Problem – Use no Rx

Medical Therapy OptionsProgestins COC (best in continuous form) Provera or Norethisterone The Mirena IUS

• Danazol & Gestrinone

• GnRH agonists +/- Add Back Therapy

• A question of side effects