Case 7 A couple who cannot conceive

 Case 7 A couple who cannot conceive

A 25-year-old hairdresser, Mina Blackburn, presented with her

28-year-old husband, Chris, an offshore engineer, because of

their inability to conceive over the last 12 months. She

stopped depo-medroxyprogesterone acetate injections

(DMPA) a year ago. She has never been pregnant before. Her

menstrual cycle is irregular. When her husband is home she

frequently uses ovulation kits. She is very anxious and feels

that there is something wrong with her. Her distress is

increased by the fact that her younger sister had a 20-week

scan showing a twin pregnancy last week.

What information should you elicit from

the history?

History from the female partner

• Menstrual history:

 detail of length and regularity of her cycle

 how was her cycle prior to using DMPA?

 how long she has been on DMPA?

 any history of dysmenorrhoea?

• Has she ever tried for pregnancy in any previous

relationship?

• History of any alterations in weight

• Past history of pelvic inflammatory diseases, Chlamydia or any other sexually transmitted infection

• Any significant past medical or surgical history or drug

allergies

• Timing and result of most recent cervical smear test

History from male partner

• Has he fathered any pregnancies before?

• How frequently he works offshore? Does he work near

heat?

• Any surgery (specifically testicular torsion, orchipexy,

appendectomy)

• Any history of mumps

History from both partners

• Intercourse: frequency, dysparunia, problems with

ejaculation

• History of smoking and alcohol use

Mina had menarche at the age of 13 years, since then she

had a regular cycle. She used the combined oral

contraceptive for contraception from the age of 16 years for

5 years but changed to DMPA as she did not have to

remember to take it. She met her present partner at the age

of 22 years and the couple decided to try for pregnancy so

Mina did not continue with DMPA. She admits that she has

gained 2stones (12.7kg) in weight over last 2 years and her

body mass index (BMI) is 33 in the clinic today. Since

coming off DMPA her periods have not been regular.

Chris has not fathered any children. He denies a history of

mumps or any genital surgery. He is fit and healthy. He

works offshore with a rota of 4 weeks off and 4 weeks on.

He does not work near heat, radiation or chemicals. The last

year has been particularly stressful for the couple as Chris

had to be away from home for much of his time onshore as

his mother has been very ill. With a change in his job plan,

he will be office-based onshore from next month.

The couple deny any problems with sexual intercourse.

They are both non-smokers and have the occasional glass of

wine.

What are the issues to consider in

this case?

Actual length of time trying for pregnancy

As Chris is away more than half of the time, the duration

of unprotected sex does not amount to 12 months. Subfertility is defined as inability to conceive after 1 year of

regular unprotected intercourse.

Obstetrics and Gynaecology: Clinical Cases Uncovered.

By M. Cruickshank and A. Shetty. Published 2009 by Blackwell

Publishing. ISBN 978-1-4051-8671-1.58 Part 2: Cases

PART 2: CASES

Mina’s weight gain

Increased BMI is associated with anovulation or ovulatory dysfunction.

Use of DMPA

Return to fertility is not immediate after coming off

DMPA. It can take up to 6 – 9 months after the last

injection.

What initial advice would you give to

the couple?

Reassurance

About 84% of couples in the general population will

conceive within 1 year if they do not use contraception

and have regular sexual intercourse. Of those who do not

conceive in the first year, about half will do so in the

second year.

With the actual length (less than 1 year) of trying

for conception this couple is still within the favourable

time zone. Chris ’ s job change to onshore gives the

couple a relatively high chance of spontaneous

conception.

Advice on weight loss

Mina ’ s irregular periods suggest infrequent ovulation.

The fact that Mina gained 2 stones in weight in

recent years can explain ovulatory dysfunction and

irregular cycles. She should be strongly advised to

lose weight. Even losing 5 – 10% of body weight can

regulate periods, enhance the chances of spontaneous

pregnancy and decreases the risk of miscarriage. In

addition, it improves general well - being. Participating in

a group programme involving dietary advice and

exercises will improve weight loss compared to advice

alone.

Intercourse

Sexual intercourse every 2 – 3 days optimizes the chance

of pregnancy. Timing intercourse to coincide with ovulation causes stress and is not recommended. Ovulation

kits are based on luteinizing hormone (LH) peak around

ovulation.

Folic acid

As Mina is trying to become pregnant she should be

advised to take folic acid (0.4 mg/day) to reduce the risk

of neural tube defects.

What further investigations should you

consider?

Male partner

Semen a nalysis

This should be the first test in infertility investigations as

up to 40% of men can have suboptimal semen parameters (as per World Health Organization reference range;

Table 7.1 ).

Female partner

Immunity to r ubella

Rubella screening is recommended so that those who are

susceptible can be offered vaccination. Women should be

advised not to become pregnant for at least 1 month following vaccination and a repeat serum sample should be

taken to confirm immunity.

Basal h ormonal p rofile

As her cycle is irregular, basal follicle stimulating

hormone (FSH), LH, prolactin (PRL), thyroid function

test (TFT) and serum testosterone tests should be

peformed. Timing of these tests need to be specified as

Table 7.1 WHO reference values for semen analysis 2000.

Criteria Reference values

Volume 2.0mL or more

Liquefaction

time

Within 60minutes

pH 7.2 or more

Sperm

concentration

20million spermatozoa per millilitre or

more

Total sperm

number

40million spermatozoa per ejaculate or

more

Motility 50% or more motile (grade a + b) or

>25% grade a within 60minutes of

ejaculation (motility is graded as a–d.

Grade a, rapid progressive motility; grade

b, slow progressive motility; grade c,

non-progressive motility; grade d,

immotile)

Morphology 15%

While blood

cells

Less than 1million per millilitreCase 7 59

PART 2: CASES

basal, that is day 1 – 5 of her menstrual cycle (day 1 is the

day of starting her period).

Transvaginal u ltrasound

Transvaginal scan of the female partner is recommended

to rule out polycystic ovaries and to have baseline assessment of her uterus.

Urinary C hlamydia t est

A urine Chlamydia test is used to screen for infection.

Chlamydia is a common cause of infertility from tubal

blockage. Chlamydia trachomatis is present in 10% of the

sexually active population aged 19 years or less. It is a

major cause of pelvic inflammatory disease, leading to

chronic abdominal pain, ectopic pregnancy and tubal

factor infertility. Asymptomatic Chlamydia infection

may go unrecognized and untreated. Although the prevalence of Chlamydia among subfertile women in the UK

is only 1.9%, uterine instrumentation carried out routinely as part of infertility investigation may reactivate or

introduce upper tract dissemination of an endocervical

Chlamydia infection, resulting in iatrogenic pelvic

inflammatory disease. DNA techniques such as polymerase chain reaction and ligase chain reaction for analysis of cervical and urine specimens are highly sensitive

and specific for diagnosing Chlamydia infection.

KEY POINT

Assessment of ovulation by mid-luteal progesterone is not

recommended as her cycle is irregular and the mid-luteal

phase cannot be determined.

KEY POINT

All patients who may require cervical instrumentation

should be screened for Chlamydia so that if present, the

infection is not exacerbated.

The couple return after 4 months. Chris works onshore all

the time. Mina has managed to lose 3kg in weight. Her

FSH, LH, PRL, TFT and testosterone are all within normal

limits. A pelvic ultrasound at the last visit

showed evidence of polycystic ovaries. Her

urine Chlamydia test is negative. Her menstrual

cycle is more regular at κ = 4–5/30–37 days.

The result of Chris’s semen analysis is

as follows:

Volume 2.0mL

Liquefaction time 45minutes

pH 7.3

Sperm concentration 18million/mL

Total sperm number 36million

Sperm motility:

grade a 10%

grade b 15%

grade c 35%

grade d 40%

White blood cell none

Morphology 7%

Chris is completely devastated to be told that

his semen parameters are suboptimal causing

infertility.

What advice will you give the couple at

this visit?

You should try to reassure the couple. The test for

semen analysis is a very poor predictor of fertility. It is a

sensitive test but the specificity is very low. An abnormal

test does not always mean true abnormality. Check

that he followed the instructions for semen analysis

correctly:

• He did not miss the receptacle for collecting the

specimen

• The couple abstained from intercourse for at least

72 hours

• Any history of recent viral illness

• The sample reached laboratory in time

• The sample was not exposed to heat or cold before

reaching the laboratory

• He is not on any medication

What should you do now?

A repeat sample should be requested at least 3 weeks

after the last sample. A single test will falsely

identify about 10% of men as abnormal, but repeating

the test reduces this to 2%. However, if the first

semen analysis is normal then there is no need to

repeat it.60 Part 2: Cases

PART 2: CASES

Now review the situation for this couple

Mina has a regular cycle now and you need to check that

she is ovulating. Ovulation is checked by mid - luteal progesterone (traditionally called day 21 progesterone). As

the length of the secretary phase is constant to 14 days,

mid - luteal progesterone has to be timed according to the

luteal phase and length of the cycle. The cycle length

minus 7 is the day mid - luteal progesterone should be

checked to detect ovulation. In this case you can start

tracking her progesterone from day 23 and can repeat it

in 7 days ’ time (as Mina ’ s cycle length = 30 – 37 days; day

23 for 30 - day cycle and day 30 for 37 - day cycle). Values

range 16 – 28 nmol/L as the lowest limit is suggestive of

ovulation. In the meantime, encourage the couple to

keep trying for a pregnancy.

Mid-luteal progesterone shows the highest value of

10nmol/L. The repeat semen analysis is as follows:

Volume 3.0mL

Liquefaction time 45minutes

pH 7.3

Sperm concentration 25million/mL

Total sperm number 75million

Sperm motility:

grade a 25%

grade b 5%

grade c 30%

grade d 40%

White blood cell none

Morphology 15%

You see the couple to discuss these

results. What information can you

give them based on the results of

their investigations?

• Repeat investigations have revealed normal semen

parameters

• Serum progesterone level indicates anovulation

• The diagnosis of polycystic ovarian syndrome is made

as per the Rotterdam criteria (international consensus).

This criterion requires the presence of two out of three

of the following criteria:

 oligomenorrhoea or anovulation

 clinical and biochemical hyperandrogenism

 polycystic ovaries on ultrasound (at least 12 follicles

measuring 2 – 9 mm in diameter and or an ovarian

volume in excess of 10 cm3)

What are the clinical implications for

this couple?

In this case the diagnosis is oligovulation or anovulation

as well as ultrasound features of polycystic ovaries.

Treatment consists of:

• Ovulation induction when the patient wishes to

conceive

• Encourage her to continue to lose weight

• Ovulation induction because a diagnosis of anovulation has been made (Box 7.1 )

Box 7.1 Ovulation induction

• Clomiphene citrate is the first line of drug for ovulation

induction in women with anovulation

• It is an anti-oestrogen and induces gonadotrophin

release by occupying the oestrogen receptors in the

hypothalamus, thereby interfering with the normal

feedback mechanism. Increased gonadotrophins

stimulate the ovaries to produce more follicles

• It is associated with the adverse effects of hot flushes,

ovarian hyperstimulation, abdominal discomfort and

multiple pregnancies

• Clomiphene is started at a dose of 50mg/day for

5days

• You need to monitor at least the first cycle by pelvic

ultrasound scan to check how many follicles are

developing

• If three or more follicles develop, you advise the patient

to use contraception in order to avoid a multiple

pregnancy

• Evidence of ovulation is checked by measuring

mid-luteal progesterone or tracking follicles on

ultrasound

• The dosage is increased in the subsequent cycle if

ovulation is not documented. Approximately 70–80%

of anovulatory women ovulate on clomiphene at the dose

of 100–150mg; however, only 30–40% become

pregnant

• If pregnancy is not achieved after three ovulatory cycles

on clomiphene, a check for tubal patency is now

indicated

KEY POINT

You do not need to check for tubal patency prior to

ovulation induction. There is nothing in the history

suggestive of tubal damage or pelvic inflammatory disease,

and her Chlamydia test was negative.Case 7 61

PART 2: CASES

CASE REVIEW

When most couples reach the fertility clinic they are very

distressed and the situation is compounded by the fact

that everyone around them seems to become pregnant

without any problems. They need an empathetic approach

rather than just a barrage of investigations. Stress is

known to reduce fertility; lifestyle modification including

weight reduction and promoting a healthy lifestyle should

be part of the initial approach while investigating for other

causes.

As all the investigations, especially semen analysis, are

very poor predictors of fertility, the couple need to be

counselled that numbers not matching with reference

range does not mean sterility. There may be other

factors responsible. However, it is reassuring if all the

investigations are normal (mid - luteal progesterone

documenting ovulation, normal semen analysis and patent

After 4 months Mina attends your clinic for review. She had

three cycles of clomiphene at 100mg, all of which have

been documented as ovulatary. However, she did not

become pregnant.

What would you do next?

You need to check the patency of her fallopian tubes

using one of the following methods.

Hysterosalpingography

This is an outpatient - based investigation in which a radio -

opaque dye is passed through the cervix and an X - ray of

the pelvis is taken to look for dye spill from the fimbrial

end of the tube. In addition, it supplies imaging information about uterine abnormality as the cavity is visualized.

Diagnostic laparoscopy and dye test

This is the gold standard for diagnosis of tubal occlusion.

It gives information on pelvic or tubal adhesions, the

presence of endometriosis and fibroids as well as determining tubal patency. However, laparoscopy involves

general anaesthesia, and is associated with a small risk of

bowel injury.

Hysterosalpingocontrast sonography

This is an outpatient - based procedure where contrast

agent is passed through the cervix and the tubes are visualized on ultrasound.

The couple decide to go ahead with a laparoscopy and

dye test. Mina is found to have a normal pelvis and both

fallopian tubes are patent. Afterwards, a plan is agreed

to continue with clomiphene citrate for further two

cycles. Following the second cycle, Mina misses her period

and a urinary pregnancy test is positive. She has a

8-week scan showing an intrauterine ongoing pregnancy

(singleton).

fallopian tubes) but it can be frustrating if there is no cause

to explain their subfertility.

Approximately 20% of the couples attending infertility

clinics fall into this category. Treatments for unexplained

infertility are largely empirical and include superovulation

and intrauterine insemination (stimulating ovaries with

gonadotrophins and timing semen insemination once

the follicle is mature). Ovulatory dysfunction is largely

treated by medical means (clomiphene citrate and/or

gonadotrophins).

If there is suspicion of tubal blockage (such as a history

of Chlamydia, or other sexually transmitted diseases),

patency of the tubes should be checked before commencing

on ovulation - inducing drugs. If tubes are blocked, in vitro

fertilization (IVF) is a more cost effective treatment than

tubal surgery.

• Clomiphene citrate is first line of treatment for ovulatory

dysfunction

• IVF is a cost effective option for tubal blockage

• Treatments for unexplained infertility are largely empirical

• There are no proven medical treatments for sperm

disorders