How to approach a case of infertility

Dr Manal BeheryAssistant professorZagazig University 2013

Definitions• Infertility = Inability of a couple practicing

frequent intercourse and not using contraception to conceive a child

Under 35 year :No conception after one year of unprotected intercourse

Over 35 year :No conception after 6months of unprotected intercourse

Types of Infertility

Primary infertility Couple Has Never Produced

A pregnancy

Secondary infertility Woman has previously been pregnant,

regardless of the outcome, and now is unable to conceive

Causes of infertility

• Tubal pathology 35%

• Male factor 35%

• Ovulatory dysfunction 15%

• Unexplained 10%

• Cervical/other 5%

Causes of tubal/ Pelvic pathology

• Congenital anomalies

• Tubal occlusion

• May occur as sequelae of– PID– endometriosis– abdominal/pelvic surgery– peritonitis

Causes of tubal/ Pelvic pathology

• Congenital anomalies

• Tubal occlusion

• May occur as sequelae of– PID– endometriosis– abdominal/pelvic surgery– peritonitis

Causes of Ovulatory Dysfunction

– polycystic ovary syndrome– hypothalamic anovulation– hyperprolactinemia– premature and age-related ovarian failure– luteal phase defect (theoretical)

Causes of male infertility:

– reversible conditions (varicocele, obstructive azoospermia)

– not reversible, but viable sperm available (ejaculatory dysfunction, inoperative obstructive azoospermia)

– not reversible, no viable sperm (hypogonadism)– genetic abnormalities– testicular or pituitary cancer

What Can I Do?

A PRACTICAL APPROCH

Counsel patient!

• In normal young couples:– 25% conceive after one month– 70% conceive after six months– 90% conceive by one year

• Only an additional 5% • will conceive in an additional 6-12 months

Councelling

Evaluating both partners is essential Couple should be informed about:

different causes of infertility tests and procedures required to make a diagnosis various therapeutic possibilities

Couple’s interview is conducted together as well as separately

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Possible causes of infertility

Start with History. . .

General and Sexual HistoryObstetric and Gynecological History

What Clues Can You Find on History?

Step1 history:General and Sexual History

General history occupation and background use of tobacco, alcohol and drugs history of abdominal surgery and earlier

diseases/infections Sexual history

sexual disturbances or dysfunction such as vaginismus, dyspareunia or erectile dysfunction

sexually transmitted infections

Obstetric and Gynecological History

Reproductive history Gynecological history Age at menarche Menstrual periods: duration and intervals Previous contraceptive use Previous testing and treatment for infertility

Step2 : General and Gynecological Examination

Visual evaluation andpelvic exam for women

to rule out:

Visual evaluation andpelvic exam for women

to rule out:

Visual evaluation andpenile exam for men

to rule out:

Visual evaluation andpenile exam for men

to rule out:

EndocrinopathyEndocrinopathy

Congenital anomaliesCongenital anomalies

Uterine hypoplasiaUterine hypoplasia

Cervical lesionsCervical lesions

DyspareuniaDyspareunia

HypogonadismHypogonadism

TumorsTumors

Epididymal cystsEpididymal cysts

CryptorchidismCryptorchidism

HydroceleHydrocele

VaricoceleVaricocele

Male Partner: Semen Analysis

Semen is studied for a number of factors including:

Volume (1.5 cc to 5.0 cc) Number of sperm present (> 20 million/ml) Sperm motility (> 60%) and forward progression

(more than 2 on scale 1 to 4) Morphology (> 60% normal forms) Presence of any infection

Semen analysis

Other Tests

Urine analysis: to rule out infection Endocrine tests: to measure concentrations of hormones testosterone, FSH

and LH Anti-sperm antibodies Sperm penetration assay: to establish ability of

sperm to penetrate egg Postcoital test (low validity): to establish ability of sperm to penetrate cervical mucus

Male partner: Evaluation:

1) Repeat semen analysis2) Physical exam- varicocele, testicular size3) Lab testing- testosterone, FSH, LH4) Genetics for special cases

IUI (intrauterine insemination)

ICSI (intracytoplasmic sperm injection)

IUI VS ICSI

Don’t wait a year if:– irregular menses;

intermenstrual bleeding– h/o PID

– h/o appendicitis with rupture

– h/o abdominal surgery– dyspareunia– age > 35– male factors

On your first visit:

• Semen analysis • Confirm ovulation

– basal body temperature charting– ovulation predictor kits (detect LH surge)– consider serum progesterone on day 21

• Labs: – TSH and prolactin. DHEA-S if concern for PCOS.– FSH & estradiol on cycle day 3 if >35y. – Cervical cultures prn.

Ovulation

Basal body temprature

Ovulation Predictor Kits

Salivary Estrogen: TCI Ovulation Tester- 92% accurate

Add Saliva Sample

Non-Ovulatory Saliva Pattern

High Estrogen/ Ovulatory Saliva Pattern

Approach to Ovulation Disorders

• Evaluate- HypothyroidismProlactin Disorder

Hyperandrogenism- PCOSWeight loss/ weight gain

• Induce OvulationClomid (clomiphene citrate)

Three months later

• Hysterosalpingogram– evaluates tubal patency and uterine cavity shape– noninvasive but involves a tenaculum– performed by radiology with gynecology supervision– diagnostic and therapeutic

Hysterosalpingogram

HSG: Unilateral Blocked Tube

HSG: bilateral tubal block

HSG: Hydrosalpinx

Diagram shows the appropriate steps in an imaging evaluation for fallopian tube abnormalities.

©2009 by

Other Tests

Laparoscopy to evaluate for pelvic disease, such as endometriosis

check patency of fallopian tubes

Hysteroscopy to evaluate condition of uterine cavity (polyps, fibroids)

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• Post coital test

• endometrial biopsy

• immune testing for antisperm antibodies

• routine cervical cultures

Traditional Infertility Evaluation

1) Semen Analysis

2) Hysterosalpingogram (HSG)

3) Documentation of Ovulation

4) Post-coital Exam

5) Diagnostic Laparoscopy

Current Infertility Evalution

1) Semen Analysis2) Hysterosalpingogram (HSG) 3) Documentation of Ovulation

4) Ovarian Reserve Testing

Ovarian Reserve Testing

Day #3 FSH (<10 mIU/ml) and estradiol (<80 pg/ml)

-Correlates with the functional status of the ovaries and the quality of the oocytes

- FSH >15 only 5% success with IVF

- High estradiol level increases risk of cancelling IVF cycle

Treatment Possibilities:Female Infertility

Ovulation disordersOvulation disorders Ovulation-inducing drugsOvulation-inducing drugs

HyperprolactinemiaHyperprolactinemia Prolactin-suppressing drugs

Prolactin-suppressing drugs

Uterine and tubal abnormalities

Uterine and tubal abnormalities Surgical proceduresSurgical procedures

Cervical mucus problemsCervical mucus problems Intrauterine inseminationIntrauterine insemination

EndometriosisEndometriosis Suppressing hormones or surgical procedure

Suppressing hormones or surgical procedure

Case 1

• A 24 year old couple comes to see you. They have been trying to get pregnant for 8 months.– What questions do you ask?

Case 1

• The woman tells you she has never been pregnant. She has a regular 28 day cycle and bleeds for 4 days each month. Her medical history is unremarkable except she “got really sick” when she was 16 and had “nasty stuff coming from down there”– what do you do next?

Case 2

• A 35 year old woman and her 31 year old male partner come to see you. They have been trying to get pregnant for 6 months.– What do you ask?

Case 2

• She says her periods have been irregular since she went off the pill a year ago. She has never been pregnant. He has fathered a child by another woman several years ago.– What do you look for on exam?– What lab tests do you order today?– Do you give them homework?

Case 2

• They come back 3 months later with BBT charts showing no discernable pattern. Lab tests, including semen analysis, were all normal.– What is the diagnosis?– What do you do next?

Case 2

• You begin discussion of clomiphene. They want to know the side effects, and if this means they’ll have sextuplets and get a free house like the folks on TV.– What do you tell them?– How do you administer the clomiphene?

Case 2

• They come back in one month. She feels “like a total bitch - excuse me, doctor” on the clomiphene. She is not pregnant. BBT charting shows a mid-cycle temperature rise.– What happens next?

Case 3

A 31-year-old G1 P1 woman presents with a history of infertility of 2-year duration.

Manarche at 12 years and occurs at28-day intervals.

A biphasic basal body temperature chart is recorded.

She denies sexually transmitted diseases, hysterosalpingogram shows patent tubes and a

normal uterine cavity. Her husband is 34 years old and his semen

analysis is normal.

➤ What is the most likely etiology of the infertility?

• ➤ Most likely etiology: Endometriosis (peritoneal factor).

• What further support the diagnosis ?

• if the patient complained of the three Ds of endometriosis (dysmenorrhea, dyspareunia, anddyschezia), then the examiner would be pointed toward the peritoneal factor.

• A 22-year-old G0 P0 woman complains of irregular menses every 30 to 65 days. The semen analysis is normal. The hysterosalpingogram is normal. Which of the following is the most likely treatment for this patient?

• A. Laparoscopy• B. Intrauterine insemination• C. In vitro fertilization• D. Clomiphene citrate

• A 26-year-old G0 P0 woman has regular menses every 28 days. The semen analysis is normal

• . The patient had a postcoital test revealing motile sperm and stretchy watery cervical mucus. She has been treated for chlamydial infection in the past.

• Which of the following is the most likely etiology of her infertility?

• A. Peritoneal factor• B. Male factor• C. Cervical factor• D. Uterine and tubal factor• E. Ovulatory factor

• A 28-year-old G1 P1 woman complains of painful menses and pain with intercourse. She has menses every month and denies a history of STD

• Which of the following tests would most likely identify the etiology of the infertility?

• A. Semen analysis

• B. Laparoscopy

• C. Basal body temperature chart

• D. Hysterosalpingogram

• E. Progesterone assay

• A 34-year-old infertile woman is noted to have evidence of blocked fallopian tubes by HSG

• Which of the following is the best next step for this patient?

• A. FSH therapy

• B. Clomiphene citrate therapy

• C. Laparoscopy

• D. Intrauterine insemination

Case 4

A 37-year-old female and her 37-year-old husband present with the complaint of a possible fertility problem. The couple has been married for 2 years.

The patient has a 4-year-old daughter from a previous relationship.

The patient used birth control pills until one-and-a- half-years-ago

. The couple has been trying to conceive since then and report a high degree of stress related to their lack of success.

Case cont’ The patient reports good health and no

problems in conceiving her previous pregnancy or in the vaginal delivery of her daughter.

She reports that her periods were regular on the birth control pill, but have been irregular since she discontinued taking them.

She reports having periods every 5-7 weeks.

Past history is remarkable only for mild depression. Imipramine 150 mg qhs for the last 8 months is her only medication

Case cont’ has no history of STDs, abnormal Paps, smoking,

alcohol or other drugs. She has had no surgery. The patient’s partner also reports good health and

reports no problems with erection, ejaculation or pain with intercourse.

He has had no prior urogenital infections or exposure to STDs

. He has had unprotected sex prior to his current relationship, but has not knowingly conceived.

He has no medical problems or past surgery

Case cont’;

He works as a long-distance truck driver and is on the road 2-3 weeks each month.

He smokes a pack of cigarettes a day since age 18 and drinks 2-3 cans of beer 3-4 times a week when he’s not driving.

He occasionally uses amphetamines to stay awake while driving at night. The couple has vaginal intercourse 3-5 times per week when he is at home.

Physical exam

The patient is 5’9” and weighs 130 pounds. Breast exam reveals no tenderness or masses,

but bilateral galactorrhea on compression of the areola.

Pelvic exam reveals normal genitalia, a well-estrogenized vaginal vault mucosa and cervical mucus consistent with the proliferative phase.

The uterus is anteflexed and normal in size without masses or tenderness.

Patient Laboratory

• Results Normal Values• TSH 2.1 mIU/ml 0.5-4.0 mIU/ml• Free T4 1.1 ng/dl 0.8-1.8 ng/dl• Prolactin 60 ng/ml <20 ng/ml• FSH 6 mIU/ml 5-25 mIU/ml• LH 4 mIU/ml 5-25 mIU/ml

• Basal body temperature chart shows a monophasic temperature graph.

Partner

• Semen analysis revealed 2 cc of semen, 4 million per mL, 30% normal forms and 20% motility.

Management

• The patient’s major infertility factor is anovulation; • the most likely cause is hyperprolactinemia from

imipramine. • The prolactin level is elevated, consistent with drug-

induced hyperprolactinemia.

• The patient was instructed, in conjunction with her therapist, to taper off the imipramine.

• Her follow-up basal body temperature chart was biphasic, consistent with ovulatory cycles.

•  

Management cont’

The patient’s partner, however, has a semen analysis that is consistent with oligospermia.

The couple was given their options of: 1) In Vitro fertilization with ISCI; 2) artificial insemination with partner’s sperm; 3) artificial insemination with donor sperm; or 4) adoption

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