Active management of infertility

Dr Aniruddha Malpani, MD

Malpani Infertility Clinic

www.DrMalpani.com

Traditional approach

• Infertility is a common problem

• Important and urgent for the patient

• However, most doctors take a “wait and watch “ approach

• Often , patients get fed up and frustrated and drop out of treatment

• This is a shame !

Need to change !

• Patients are getting married at an older age – time is running out as the biological clock ticks on

• We now have technology to help them !

Common mistakes – what not to do !

• The couple is not seen together.

• Husband’s semen analysis not performed.

• Investigations are performed in a piecemeal fashion rather than as part of an overall strategy.

• These are often done in a slow, time-consuming manner and patients get fed up

Common mistakes – what not to do !

• When the patient changes doctors, the doctor insists on repeating all the tests again, wasting the patient’s time and money

• Doctors are keen to “do something” and repeated curettages and laparoscopies are often done unnecessarily

Common mistakes – what not to do !

• Also, myomectomies may be performed for small fibroids; ovarian cystectomy and wedge resections done for simple ovarian cysts which should have been left well alone; as well as “uterine ventrisuspension” when all else fails.

• These create more damage and often cause infertility !

Wasteful tests

• TORCH test

• TB PCR

• Hysteroscopic “ metroplasty”

• NK cell testing for failed implantation

The harm done

• Trust between the doctor and patient breaks down.

• The temptation to try many empirical, possibly useless medical treatments is considerable

• Patients often end up spending large sums of monies at the hands of quacks and “spiritual healers”.

What to do

• The couple must be seen together and treated as a unit.

• First, find out the reason for the infertility.

• The workup ( testing protocol) must be explained to the patient and should be completed in 2 months.

Egg plus sperm = baby !

A cost-effective testing strategy

Need only 4 things to make a baby !Test for

• Eggs• Sperms• Uterus• Tubes !

A cost-effective testing strategy

Semen analysis (during the wife’s menstrual period)

Blood tests ( AMH, Prolactin, LH, FSH, TSH) – Day 3-5;

Hysterosalpingogram-Day 5-7;

Ultrasound for ovulation monitoring – Day 11-16.

A cost-effective testing strategy

• Laparoscopy NOT needed to complete the workup

• Low yield when HSG is normal

A cost-effective testing strategy

•  The testing should not stop when a problem is discovered. Complete the testing. Couples may have multiple problem.

• A single abnormal result does not necessarily mean that a problem exists – re-test to confirm.

Plan of action

• After the workup, plan course of action.

• Treatment should not be on an ad-hoc single cycle basis

Plan of action

• You need to keep on progressing to more aggressive treatment!

• Similar to the stepped-care approach to treating hypertension !

Unexplained infertility

• Timed intercourse, 6 cycles, for young couples

• Intrauterine insemination (IUI)- 3 cycles;

• Superovulation with HMG plus IUI-3 cycles;

• then IVF.

• Don’t waste time!

Treatment plan

• As a rule of thumb, if a treatment is going to work, it should work in 4 cycles.

• Don’t repeat IUI again and again

• Need to tailor treatment according to patient’s age, medical diagnosis, and budget

Semen analysis

• Easy test to do - easy to do badly !

• Must be performed at a reliable lab

• 3-day abstinence

• No lubricant

• Clean wide-mouthed jar

Semen analysis

• Often, men are forced to produce a semen sample in a dirty bathroom, and this can be hard !

• Patient may need help to produce a sample – discuss this with him

• Can use a vibrator for assistance

Semen analysis

Interpreting the report

• Volume

• Sperm count – million per ml

• Motility

• Total motile sperm count in ejaculate

Semen analysis

Tips in interpreting the report

• Fructose and pH of importance only in men with azoospermia

• A few pus cells are normal – treatment with antibiotics is not usually helpful !

Azoospermia

Determine the reason

Obstructive ?

Non-obstructive ?

Clinical examination ( vas, epididymis, testis size)

Volume, pH, fructose

FSH level

Testis biopsy

1. Diagnostic – need multiple microbiopsies to sample many areas !

2. Send in Bouin’s fluid to reliable lab3. Spermatogenesis is not uniform, and some

patients with testicular failure ( non-obstructive azoospermia) will have isolated foci of sperm production which can be used for TESA-ICSI

Low sperm count

Reason often unknown

Maybe because of a microdeletion on the Y-chromosome. Not worth doing this test – does not change treatment options

Empiric medical therapy – wastes time and money

Varicocele surgery not helpful

Low sperm count

• Knee-jerk response – refer to urologist. Usually, not helpful

• Patients get fed up

• The end-point is not an increase in the sperm count – it is a baby !

• Better to refer to IVF clinic before wife becomes old

Low sperm count

1. If total motile sperm count more than 20 million, then IUI ( with HMG superovulation)

2. If TMSC less than 5 million, then ICSI

Low sperm count

IUI is not sensible treatment for low sperm counts, though it is often misused for this !

If the sperm are not functionally competent, then washing them will not help !

Interpreting a low sperm count is difficult

Patient does not want to know what the count or motility is – he wants to know if his sperm can make a baby

Not possible to answer this – no test for sperm function

Low sperm count

We have all seen men with low sperm counts who have fathered a baby

This is why counselling these couples is difficult

IVF is the definitive test of sperm function !

Low sperm count

2 key concepts

• “ Trying time”

• Fertility potential of couple

Common mistakes in treating female infertility

1. Repeating clomiphene again and again

2. Not monitoring ovulation induction therapy

3. Using danazol to treat mild endometriosis

Tubal infertility

1. TB . Advise IVF

2. Hydrosalpinx . Advise IVF. Results with surgery very poor.

3. Cornual block. Advise FTR ( fluoroscopic tubal recanalisation)

PCOD – polycystic ovarian disease

• Commonest cause of anovulation

• Irregular cycles

• Patients often are obese and hirsute

• Vaginal scan for antral follicle count

• LH, FSH ratio

• AMH levels

PCOD – polycystic ovarian disease

• Induce ovulation

• Metformin, 1500 mg daily

• Myoinositol, 2 g daily

• Clomiphene/ Letrozole

• HMG

• Laparoscopic ovarian cauterisation

ART – Assisted Reproductive Technology

Simple principle - increase the chances of the egg and sperm meeting

What is not happening in the bedroom, we do in the lab !

IVF is the final common pathway – bypasses all hurdles !

Not artificial – we are just assisting nature !No increased risk of birth defects

But IVF is too expensive !

Maybe.

But just because the right treatment is expensive, does not mean that you do the wrong treatment, just because it is cheap !

Often, IVF is more cost-effective !

Where should I refer my patients for IVF

• Good clinic vs Bad clinic

• Embryo photos !

What is your success rate ?

• For the patient, success means a baby ! Success rate is either 100% - or 0%

• For the clinician, it’s a little more complicated , since you are dealing with groups of patients.

• Success rates have improved dramatically in the last few years !

Factors affecting pregnancy rates

• Patient ( age, cause of infertility)

• Clinic

1. Laboratory ( the IVF lab is the heart of the IVF clinic !)

2. Physician

IVF cycle

4 basic steps

• 1. Superovulation

• 2. Egg collection

• 3. In vitro fertilisation

• 4. Embryo transfer

IVF cycle1. Superovulation

1. With HMG ( gonadotropins)

Natural hormones. Urinary products

Newer recombinant preparations much more expensive, but no better

2. Downregulation with Buserelin ( GnRH) or antagonists. Both work as well

3. Low cost – clomiphene plus HMG

IVF cycle Superovulation

Monitor follicular growth ( ovarian response)

Vaginal ultrasound scans

– Day 3, 10, 12, 14

Rarely need to measure E2 levels !

IVF cycle

2. Egg collection

Vaginal ultrasound guidance

Non-surgical

In vitro fertilisation

100000 sperm added to egg

Kept in CO2 incubator ( 37 C) – heart of an IVF lab !

IVF cycle

4. Embryo transfer

Number of embryos ?When to transfer ? Day 2 or 3 or 5 ?

IVF cycle

No need for bed rest – you cannot cough the embryo out !

Still a matter of luck !Not the patient’s “fault” if she doesn’t

conceiveShe cannot “reject” the embryo !

Risks of IVF

1. No pregnancy2. Multiple pregnancy3. Ectopic pregnancy4. OHSS – ovarian hyperstimulation

syndrome. Managed conservatively

Advanced fertilisation techniques

• Intracytoplasmic Sperm Injection(ICSI)

• Assisted Hatching• Blastocyst transfer

• Preimplantation Genetic Diagnosis (PGD)

ICSI

• Microinjection ( Intracytoplasmic sperm injection)

• One egg + one sperm = one embryo !

• Can use testicular sperm even from men with testicular failure ( with high FSH levels and small testes)

Indications for assisted hatching

• Advanced maternal age

• Thick zona

• Repeated implantation failure

Blastocyst transfer

• Higher implantation rate ?

• The number of embryos transferred can be reduced without risking a decline in pregnancy rates . This helps to reduce the risk of multiple pregnancy .

Freezing - cryopreservation

Vitrification

• Can store and preserve–Sperm

–Embryos

–Eggs

–Ovarian tissue

The promise of ART

We can help any couple to have a baby, no matter what their medical problem !

Third party reproductionEmbryo adoptionDonor eggsSurrogate uterus

ART is a medical success story !

• However, advances in IVF have come with government guidelines and laws

• The purpose of these guidelines is to ensure that these technologies are used safely and responsibly

• How well do they work ? What purpose do really serve ?

Useful regulation

• Most doctors would agree that there is a need to regulate the practice of IVF, so that all IVF clinics meet certain basic standards.

• Need to protect infertile patients, who are emotionally vulnerable, and can get cheated easily by unscrupulous doctors

In real life

• Bureaucrats only understand paperwork

• Overburdened doctors end up spending more time filling up forms rather than talking to patients !

• Good doctors don’t need to be

monitored; and monitoring

bad doctors does not help !

Real life problem - How many embryos to transfer ?

• Ideal would be one. However, the technology is still not perfect

• The law is blind – limit of 2 for everyone !

• Why ? Makes sense for the NHS !

• Does this make sense for a 43 year old woman doing her 5th IVF cycle ?

• Let the couple decide for themselves – weigh the pros and cons

The doctor-patient relationship

• Guide your patient – help them to become an expert on their problem

• Discuss all their options with them, including

Child-free living

Adoption

Medical treatment

The ideal doctor

• Doesn’t tell the couple what to do

• Let’s them decide for themselves, so they have peace of mind they did their best !