68-Infertilitas

INFERTILITY

Dr. dr.Nusratuddin Abdullah, SpOG(K),MARS

Department of Obstetrics and GynecologyMedical Faculty – University of Hasanuddin

MAKASSAR

Definitions

InfertilityWHO: inability to conceive after two year of

regular unprotected intercourse.AFS : inability to conceive after one year of regular

unprotected intercourse. Fertility

– Ability to conceive Fecundity

– Ability to carry to delivery

Cumulative pregnancy rates

50% 75% 87 ½%

5 Months 10 Months 15 Months

DEFINITION OF INFERTILITY

Statistics 80-85% of couples will conceive within 1

year of unprotected intercourse ~90% will conceive within 2 years of

unprotected intercourseOrigin:

– Female factor ~40%– Male factor ~40%– Combined ~20%

INFERTILITY MANAGEMENT

COUPLE MANAGEMENT

FEMALE

GYNECOLOGY

MALE

ANDROLOGY

INSIDENCE Country - Developed : + 5 - 8 %

- Developing : + 30 % WHO : + 8 - 10 % (+ 50 - 80

million) couples in the world

Indonesia : + 12 % (+ 3 millions) References : + 15 % ( 1 out of 7 couples)

ClassificationPrimary Infertility: Never pregnant

Secundary Infertility: Had previous pregnancies

Idiopatic/Unexplain infertility

ETIOLOGY OF INFERTILITY

Sperm Factor

Cervical Factor

Uterine FactorOvulation Factor

Tube and Pertoneal Factor

Etiologies

Sperm Factor 25-30% Ovulation Factor 15-20% Tubal/Peritoneal Factor 25-40% Uterine Factor 5-10 Cervical factor 2-5% Unexplained 10-15%

INFERTILITY FACTORSIN

FERT

ILIT

YIN

FERT

ILIT

Y

Factors :Factors :- Age- Age- Emotional- Emotional- Environment- Environment- Freq. / Time- Freq. / Time of Coitusof Coitus- Social - Social EconomicEconomic UterusUterus

PPRREEGGNNAANNCCYY

Tube &Tube &PeritoneumPeritoneum

CervixCervix

OvulationOvulationSpermSperm

Treatment :Treatment :• MedicalMedical• SurgicalSurgical• CombinationCombination• ARTART

TUBAL FACTORS

25 - 40 %

The most frequent causes:•P.I.D. / S.T.D•SepticAbortion•IUD•Previous pelvic / tube operation•Apendicitis with perforation

AGE - INFERTILITYAGE - INFERTILITY

OOCYTES POOL

MUTATION

SENSITIVITY TO GONADOTROPHINE

Age over 35 years :

Depletion of ovarian follicular pool Meiotic and mitotic error

Oocytes quality ↓

Oligo / amenorrhea / DUB

Menstrual disturbances Ovulatory dysfunction

Leon Speroff and Frits marc A. Clinical Gynecologic Endocrinology and Infertility. Ed. VII TH. Lippincott Williams & Wilknis Philadelphia (2005) p : 1013 - 1056

AGING AND REPRODUCTION IN WOMEN

% of maximum fertility Miscarriage rate (%)

100

80

60

40

20

0

50

40

30

20

10

020-24 25-29 30-34 35-39 40-44

% of maximum fertilityMiscarriage rate (%)

INFERTILITY

COMPLICATED

MULTIPLE FACTORS IN BOTH MALE AND FEMALE MORE THAN 1 FACTORS IN EITHER MALE OR FEMALE

OVULATION FACTORS

15 - 20 %

• Genetic disorders• Hiperprolaktinemia• Hipo/Hiper tiroid• Stress• Weight Changes• Polycystic Ovary

2 - 5 %

•Anatomic disorders: retroversion, long servix,stenosis• Infection : ureoplasma• Immunologic factor: antibodi antisperm

SERVICAL FACTORS

5 - 10 %

UTERUS FACTORS

• Anatomic disorders :• Congenital• Intrauterine adhesion• Myoma uteri• Endometrial damage

• Endometrial polip• Hyperplasia of endometrium

25 - 40 %

PERITONEUM / ENDOMETRIUM

• Endometriosis• Minimal & mild Unclear• Severe adhesion and anatomic distortion

• Disturbing follicular maturation• Disturbing Ovum pick up• Transportation disorder of fertilized ovum• Toxic effect of peritoneal fluid

SPERMA • Infeksi• Kekebalan • Hormonal• Idiopati

Terganggu

Fungsi- Tempat embrio Tumbuh- Memberi makan

Terganggu

Terganggu

Terganggu

Terganggu • Tumor

• Infeksi• Gangguan Pertumbuhan

• Infeksi• Endometriosis• Kel. Bawaan

Fungsi

Fungsi

Fungsi• Ovum Pick-Up• Transportasi• Pertumbuhan embrio • Sel Telur • Kel. Hipotalamus

Pituitari• Hub. Umpan Balik• Ovarium

• Pintu • Depo Makan• Reservoir• Klep Biol.

• Infeksi• Kekebala

n• Polip• Anatomi

EXAMINATION

– History– Physical examination– Sperm analysis– Detection of ovulation– Post Coital Test– USG– HSG– Laparoscopy

The pace and extent of evaluation

should take into account :

• The couple’s wishes

• Patient age

• Duration of infertility

• Unique feature of the medical history

and physical examination

HISTORY

History-General

Both couples should be present Age Previous pregnancies by each partner Length of time without pregnancy Sexual history

– Frequency and timing of intercourse– Use of lubricants– Impotence, anorgasmia, dyspareunia– Contraceptive history

History-Male

History of pelvic infection Radiation, toxic exposures (include drugs) Mumps Testicular surgery/injury Excessive heat exposure (spermicidal)

History-Female

Previous female pelvic surgery PID Appendicitis IUD use Ectopic pregnancy history Endometriosis

History-Female

Irregular menses, amenorrhea, detailed menstrual history

Vasomotor symptoms Stress Weight changes Exercise Cervical and uterine surgery

Physical Exam-Male

Size of testiclesTesticular descentVaricocoeleOutflow abnormalities

(hypospadias, etc)

Physical Exam-Female

Pelvic masses Uterosacral nodularity Abdominopelvic tenderness Uterine enlargement Thyroid exam Uterine mobility Cervical abnormalities

PHYSICAL EXAMINATION

• Bodyweight, BMI• Thyroid Enlargment• Breast Secretions• Sign of Androgen Excess• Pelvic tenderness• Vaginal discharge• Uterine size, adnexal mass, cul-de-sac mass

Semen Analysis

Collected after 48 hours of abstinenceEvaluated within one hour of

ejaculationIf abnormal parameters, repeat twice, 2

weeks apart

Normal Semen Analysis- Volume ≥ 2cc(>1.5cc)– Concentration > 20 mill/cc

(>15 million/cc)– Morphology > 40 %

(>4%)– Motility > 60 %

(>32%)

OVULATORY FACTORS

Ovulatory dysfunction commonly results in gross menstrual disturbances : - Oligo / Amenorrhea - Dysfunctional Uterine Bleeding

The Underlying cause should always be sought :

• Thyroid Disease• Hyperandrogenism• Extreme of weight loss• Hyperprolactinemia• Obesity• Etc

METHODS FOR INVESTIGATION

• Menstrual history• Basal body temperature : - Simple and in expensive method - Biphasis patterns• Serum Progesterone• Urinary luteinizing hormone• Endometrial Biopsy• Serial Transvagianl Ultrasound• Other Evaluation - FSH - Clomiphen Citrate Challenge test

Detection of ovulation –TRANSVAGINAL USG

•ø DOMINANT FOLLICLE 18-24 mm

UTERINE FACTORS

Abnormalities of Uterine Anatomi Function

Relatively uncommon Causes of infertility

Methods for Investigation

• HSG : Defines the size and shape of the uterine cavity and will reveal developmental anomalies ( unicornuate, Septate, bicornuate uteri polyps, submucous myoma )• Ultrasound • Sonohysterography (High sensitive method for diagnosis of polys, subsemucous myoma)• Hysteroscopy (Definitive method for evaluation of uterine cavity)

Tubal Occlusive disease is an important cause of infertilityThe methods for evaluation :

Complementary and not mutually exclusive

HSGLaparoscopy and ChromotubasiHysteroscopySaline Infusion Sonography

Hysterosalpingography (HSG)

Radiologic procedure requiring contrast Performed optimally in early proliferative phase

(avoids pregnancy) Low risk of PID except if previous history of PID

(give prophylactic doxycycline or consider laparoscopy)

Oil-based contrast– Higher risk of anaphylaxis than H2O-based– May be associated with fertility rates

Hysterosalpingography (HSG)

Can be uncomfortable Pregnancy test is advisable Can detect intrauterine and tubal disorders

but not always definitive

TUBE & PERITONEUM

DIAGNOSIS

HSGHSG

NORMAL

HSG LAP. DX

HYDROSALPHINXHSGLAP. DX

SIS

Abnormalities of cervical mucus productionSperm – mucus interaction

Rarely identified asThe sole or principal Cause of infertility

Post Coital Test

Performed as closely as to the time of ovulation 6-10 hours after intercourse ≥ 10 motile sperm / field

PERITONEAL FACTORS

• Endometriosis• Pelvic / Adnexal Adhesions

May contribute to reproductive failure

Ultrasound Laparoscopy : Direct visual examination

Peritoneal Factors Endometriosis

– 2x relative risk of infertility– Diagnosis (and best treatment) by laparoscopy – Can be familial; can occur in adolescents– Etiology unknown but likely multiple ones

• Retrograde menstruation• Immunologic factors• Genetic• Etc

– Medical options remain suboptimal

Laparoscopy

Invasive; requires OR or office setting Can offer diagnosis and treatment in one setting Not necessary in all patients Uses (examples):

– Lysis of adhesions– Diagnosis and excision of endometriosis– Myomectomy – Tubal reconstructive surgery

54 A/Prof R Gyaneshwar

Lap / Dye

DIAGNOSIS FAKTOR PENYEBABDIAGNOSIS FAKTOR PENYEBABINFERTILITASINFERTILITAS

AN. SPERMAAN. SPERMA

UPSUPS

- VT- VT- HSG- HSG- LAP DX- LAP DX- HISTEROSK.- HISTEROSK.- TEST- TEST

RUBINRUBIN-HSGHSG- LAP DX- LAP DX

- SIKLUS- SIKLUS HAIDHAID- BBTBBT- LSLS- BIOPSIBIOPSI ENDOM.ENDOM.- OVA TEST- OVA TEST- USGUSG- PX HORMON - PX HORMON

UNEXPLAIN INFERTILITY

DEFINITION

A couple whose routine ( standard , basic ) investigations of infertility showed no abnormality

( RRCOG guidelines 1998 )

UNEXPLAINED INFERTILITY

1. When all standard clinical investigation yield normal result ( semen analysis, PCT, Ovulation, tubal patency )

2. Estimated 10 – 15 % of infertility couples

3. Will ultimatetely reach this clinical diagnosisand using normal findings on laparoscopy, may beless than 10 %

Unexplained Infertility 5-10% of couples Consider PRL, laparoscopy, other hormonal tests, cultures,

ASA testing, SPA if not done Review previous tests for validity Empiric treatment:

– Ovulation induction– Abx– IUI– Consider IVF and its variants

Adoption

INFERTILITY MANAGEMENT: Medication Reconstructive surgery Assisted Reproductive Technology

(ART)

Barbieri Robert L. : Female InfertilityIn Yen and Jaffe’s Reproductive Endocrinology. Ed V Th Elsevier Saunders. Philadelphia.2004. P : 633- 668

Identify allIdentify allFertility factorsFertility factors

ExpectantExpectantManagementManagement

CC or CC or CC - IUICC - IUI

hMG orhMG orhMG-IUIhMG-IUI

IVFIVF

Correct allCorrect allFertility factorsFertility factors

Increasing intensiveness of resource utilization

Incr

easi

ng F

ecun

dabi

lity

Figure 20 – 16. Staircase approach to empirical infertility treatment/ For women over 35 years old, the first three steps in the algorithm should be rapidly completed. In women less than 30 years old, more time can be spent on the first three steps in the staircase

35 Years

INFERTILITY FACTORSINFERTILITY FACTORS

HEALTH SERVICEHEALTH SERVICEFACILITIESFACILITIES

SOCIALSOCIALECONOMICECONOMIC

Management & Management & Treatment ProgramTreatment Program

AGE AGE (Wife)(Wife) Patient

Wishes

Duration of

Duration of

InfertilityInfertility

MEDICATIONUsing ovarian stimulation drugs

(Ovulation Induction):

Clomiphene Citrate (CC) Human Menopausal Gonadotrophine (HMG)

Ovulation Induction

CC– 70% induction rate, ~40% pregnancy rate– Patients should typically be normoestrogenic– Induce menses and start on day 5– With dosages, antiestrogen effects dominate– Multifetal rates 5-10%– Monitor effects with PK, pelvic exam

hMG (Pergonal)

LH +FSH (also FSH alone = Metrodin) For patients with hypogonadotrophic

hypoestrogenism or normal FSH and E2 levels Close monitoring essential, including estradiol

levels 60-80% pregnancy rates overall, lower for PCOS

patients 10-15% multifetal pregnancy rate

ARTIntra Uterine Insemination (IUI)

Invitro Fertilization (IVF)

Intra Cytoplasmic Sperm Injection (ICSI)

PRECONDITIONS FOR IUI

1. Ovulation + , either by herself or through medication

2. Normal passage through uterus & tuba

3. Semen must contain a sufficient quantity of suitable sperm cells

IVF

ICSI

INFERTILITY MANAGEMENT

SPERM ANALYSIS

NORMAL( > 20 mll/cc )

10-20 mll/cc < 10 mll/cc< 10 mll/cc < 5 mll/cc

natural

IUI.

IVF

ICSI

++++++++

++++++++ ++ ++

-- ---

±±±

Infertility Couples

• Coitus History• Utilization Drug History

• Emotional / Stress• Reproduction History

FEMALE MALE

History & Phisical Exam. • Age• History : - PID - IUD - Pelvic Op. - Dysmenorrhea - Dyspareunia - Adnexa Tumor• Genital Pathology

• Menstrual Cycle (Oligo / Amenorrhea)• Hair Growth / Hirsutism• Galactorheea • Obesity (BMI)• Congenital Anomali

HSG BBT

Abnormal Normal

Laparoscopy / Hysteroscopy

Normal

Ov. Induction IUI

6 MonthsFailed IVF -ET

Abnormal

Uncorrect ProbableCorrected

Unpregnant

Conservative6 Months

Biphasic Monophasic

Evaluation ofOvulation Disorders

PCT

Good Poor

Repeated PCTWith EE Therapy

EB

DFL Normal

CC

Recontruction Op. ConservativeOv. Induction IUI

18 Months

Failed IUI 6 Months

Good Poor

Factors : - Cervic - Husband - Immun - Sexual Dysf.