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Prof.Dr.Sezai ŞAHMAYİ.Ü.Cerrahpaşa Tıp Fakültesi Kadın hastalıkları ve Doğum

ABDReprodüktif Endokrinoloji Bilim Dalı

www.sahmay.com

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INFERTILITY: DefinitionsINFERTILITY: Definitions

Infertility:

failure to achieve conception over a 12-month period of unprotected intercourse

Primary infertility:

never having had a live birth

Secondary infertility:

failure to achieve a live birth after having had a live birth previously

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Age and FertilityAge and Fertility

Klein NA et al.:Clin Obstet Gynecol 41:912, 1998

20-24 30-34 35-39 40-440

10

20

30

40

50

60

70

6

15

30

64

%

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Infertility: factsInfertility: facts

Number of infertile couples globally - >100 million.

Associated with :

• - Female factor * 40%

• - Male factor * 30-40%

• - Common to both partners * 15-20%

• - Unexplained 5-10%

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Risk factorsRisk factors

• Age

• Tobacco smoking

• Alcohol use

• Being overweight ( BMI>35 )

• Too much exercise

• Caffeine intake

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3.Uterus faktörü

1.Spermin ulaşamaması

2.Yumurtlama olmaması

4.Tüplerin kapalı olması

Başlıca infertilite nedenleri

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Causes of Female InfertilityCauses of Female Infertility

• vaginal

• cervical

• uterine

• pelvic

• ovarian

• other causes

• unexplained

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Causes of female infertilityCauses of female infertility

• Fallopian tube damage or blockage

• Endometriosis

• Ovulation disorders

• Hyperprolactinemia

• Polycystic ovary syndrome (PCOS)

• Early menopause

• Uterine fibroids

• Pelvic adhesions

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coital difficulty

• vaginismus

• vaginal obstruction

• imperforate hymen

• absence of the vagina

• vaginal septum

• gynetresia

• poor erection

• impotence

• premature ejaculation

Vaginal causes

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cervical infertility

It involves inability of the sperm to pass through the mouth of the uterus due to damage of the cervix.

Causes include the following:

a) Inadequate or inhospitable cervical mucous

b) Cervical narrowing or "stenosis"

c) Infections of the cervix with common sexually transmitted diseases (Chlamydia, gonorrhoea, or trichomonas, as well as mycoplasma hominis and ureaplasma urealyticum)

d) Immune attack of sperm or "sperm allergy" (Antisperm antibodies)

Cervical causes

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by Leonardo da Vinci of uterus with fetus, circa 1510.

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• Anatomic problems (polyps, uterine fibroids, abnormal shape of the uterus, septum or "dividing wall" within the uterus)

• Thin or abnormal uterine lining

• Asherman’s syndrome

Uterine causes

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Tubal DiseaseTubal Disease

•Pelvic Infections•Endometriosis•Pelvic Surgery

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Pelvic causes

Include any disruption of the normal pelvic anatomy: Scar tissue or "adhesions"

Endometriosis

Blocked, scarred, or distorted fallopian tubes, dysfunctional FT.

Pelvic causes

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Pelvic inflammatory disease (PID) and infertility

Pelvic inflammatory disease (PID) and infertility

Infection of the pelvic organs that cause severe illness and may

lead to tubal blockage and pelvic adhesions leading to infertility

A common sequel to STDs, post-partum and post-abortal

infections and some systematic infections e.g. tuberculosis,

schistosomiasis PID episodes percent

0 1%

1 8%

2 22%

3+ 41%

The risk of tubal factor infertility increases

with each successive episode of PID

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EndometriosisEndometriosis

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Ovarian Failure PCOS Anovulation Poor ovarian

reserve Premature

Menopause Luteal dysfunction Gonadal dysgenesis Ovarian Cancer

Ovarian Causes of Infertility

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Cultural and social factorsCultural and social factors

Female genital Mutilation

Early age at marriage or sexual intercourse

Multiple sexual partners (Risk of genital infection)

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Preventable causesPreventable causes

Infections–STI:

Gonorrhoea,

Syphilis Etc.

Chlamydia,

Infectious And Parasitic Diseases:

Tuberculosis,

Schistosomiasis,

Sickle Cell Disease.

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Health care practices and policies

Unhygienic obstetric practices

Septic abortion and their complications

Postpartum and postabortal complications

Exposure to potentially toxic substances in:

Environment: arsenic, aflatoxins, pesticides

Diet: caffeine, tobacco, alcohol

Electro-magnetic radiation

Gamma, x-rays etc

Preventable causesPreventable causes

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PreventionPrevention

Male:

• Avoid alcohol, tobacco and street drugs

• Avoid hot tubs and steam baths

Female:

• Avoid alcohol, tobacco and street drugs

• Exercise moderately

• Avoid weight extremes

• Limit caffeine

• Limit medications

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Time Required For Conception

Fertility:One year of unprotected coitus without conception Affects 10-15% of couples in reproductive age group

Time of Exposure % pregnant

3 months 57%

6 months 72%

1 year 85%

2 years 93%

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When should a work-up begin?

When should a work-up begin?

• Most people need no treatment

• 3 year rule–5% decrease per year in

age –15-25% per year of infertile

• > 35yrs don’t wait• Obvious reasons

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History and PhysicalHistory and Physical• Sexual History – coital frequency

• Gynecologic History

– menstrual history, pelvic pain, pelvic infections, endometriosis

• Obstetric History

• Medical History

– Thyroid abnormalities, hair growth and acne, nipple discharge

– Childhood illnesses, chicken pox, German measles

• Medications

• Surgical History

– Abdominal and pelvic surgeries

• Social History / Family History

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Investigations of Infertile CoupleInvestigations of Infertile Couple

• Semen qualitative analysis (sqa)

• Basal Body Temp. charts

• Tubal patency tests (HSG)

• Hormonal tests

• Ultrasonography

• Laparoscopy

• Hysteroscopy

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Bicornate Polyp

Early Prolif Late Prolif Mid secr

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Ovulatory dysfunction

Polycystic Ovary

Syndrome (PCOS) 70%

Hyperprolactinemia 10%

Premature ovarian failure 10%

Hypothalamic amenorrhea 10%

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FOLİKÜLERMATÜRASYON

OVÜLASYON

LÜTEİNİZASYON

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Infertility: Ovarian FactorInfertility: Ovarian Factor• Menstrual History: 97.7% predictor• BBT

– Thermogenic potential of progesterone (.4-.8)

– Ovulation when see rise (1-5 days after)

– 12 or more days to menses• Progesterone 3-4 ng/mL

– 7-8 days post ovulation– Luteal phase function

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• Basal Body Temperature• Temperature increases as a result of progesterone

production in the luteal phase of the cycle

• Coincides with an increase in the progesterone level above 4 ng/ml

• A biphasic pattern signifies ovulation

• Temperature taken upon awakening

• Predicts the LH surge only within 2-3 days

First day of the period

Fertile period

Peak luteal P4 level

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Document Ovulatory Function

• Basal Body Temperature

• Ovulation Predictor Kits

• Day 22-24 Progesterone– Midluteal phase >

3ng/ml

– Preferably >10 ng/ml

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Velde ER, et al., Maturitas 30 (1998) 119-125

The Declining Follicle Pool

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• Basal hormonlarFSHÖstradiolİnhibin-BAntimüllerien hormon (AMH)

• Ultrasonik parametrelerAntral Folikül sayısıOver Volümü

• Dinamik testlerCCCT (Clomiphene challenge test)EFORT (Exogenous FSH ovarian reserve test)GAST (GnRH agonist stimulation test)

Over reservinin değerlendirilmesi Over reservinin değerlendirilmesi

Johnson NP et al.:BJOG; 113:1472, 2006

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AMH düzeyi, gebelik oranları ile pozitif ilişkilidir

Sahmay S, Demirayak G, Guralp O, Ocal P, Senturk LM, Oral E, Irez T J Assist Reprod Genet. 29:589–595, 2012

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Over cevabı-AFS ve AMHOver cevabı-AFS ve AMH

Nelson SM.:Fertil Steril, 2013

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PRL levels and Clinical findingsPRL levels and Clinical findingsH

yperp

rola

ctin

em

ia

AmenorrheaHypoestrogenism

osteoporosis

Anovulation-infertility-polimenorrhea-oligomenorrhea

Luteal phase defect

-infertility-short menstrual cycle

Şahmay, S: Temel Kadın Hastalıkları ve doğum Bilgisi, 1996

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Cervical FactorCervical Factor• Postcotial test (Sims-Huhner)

Intercourse (2-12 hrs) for testLook at: pH, Sperm, Spinnbarkeit, FerningCellularity, Sperm Shaking, sperm

AgglutanationHas seen better days

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Tubal FactorTubal Factor• Risk factors

–PID; 12%,24%,75%, Ectopic 6 fold

• HSG–2-5 days after menses–1-3 % infection rate high risk– Increase preg rate –False positive obstruction rate

(15-30%)

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Hydrosalpinges

Myoma

Normal HSG

Anatomic Evaluation Hysterosalpingogram (HSG)

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LaparoscopyLaparoscopy

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Hysteroscopy

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İnfertilitede Tedaviİnfertilitede Tedavi

• Doğru tanı

• Uygun tedavi seçimi

• Yeterli süre tedavi

• Tedavi maliyetinin düşünülmesi

• Çiftin bilgilendirilmesi

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Gebeliği etkileyen FaktörlerGebeliği etkileyen Faktörler

1. Yaş

2. İnfertilite süresi

3. İnfertilite nedeni

4. Biyolojik belirteçler (AFS, AMH, FSH)

5. Diğer

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İnfertilitede Tedavi Seçenekleri

İnfertilitede Tedavi Seçenekleri

• Bekle gör

• Ovülasyon belirlenmesi ve ilişki

• Ovülasyon uyarılması

• İntrauterin inseminasyon

• Cerrahi tedavi

• Yardımla üreme teknikleri

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Ovülasyon İndüksiyonu - TarifOvülasyon İndüksiyonu - Tarif

Ovülasyon İndüksiyonu(Anovülatuar infertil kadınların tedavisi)

Anovülatuar hastalarda, folikül matürasyonu,rüptürü ve fertilize olabilecek nitelikte

oosit oluşumu amacıyla farmakolojik ajanların kullanımı.

Kontrollü Ovarian Hiperstimülasyon(Ovülatuar kadınlarda süperovülasyon)

Ovülatuar veya Anovülatuar hastalarda, Çok sayıda folikül matürasyonu,rüptürü ve fertilize olabilecek nitelikte oosit oluşumu amacıyla farmakolojik ajanların yoğun olarak kullanımı.

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İntrauterin İnseminasyon (İUİ)

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Yardımla Üreme TeknolojileriYardımla Üreme TeknolojileriAH (Asisted Hatching)

IVF (In Vitro Fertilization)

GIFT (Gamete Intrafallopian Transfer)

PROST (Pronuclear Stage Tubal Transfer)

TET (Tubal Embryo Transfer )

ZIFT (Zygote Intrafallopian Transfer )

ICSI (Intracytoplasmic sperm injection)

MESA (Microepididymal sperm aspiration)

PESA (Percutaneous epididymal sperm aspiration)PGD (Preimplantation genetic diagnosis)

TESE (Testicular Sperm Extraction)

TET (Tubal embryo transfer)

ZIFT (Zygote intrafallopian transfer)

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IVF-ET (Tüp Bebek)IVF-ET (Tüp Bebek)

EmbriyoTransferi

ET

Yumurta toplanması

OPU

Yumurtalıkuyarılması

COH

Vücut dışındaDöllenme

IVF

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Aspirasyon yoluyla Sperm Elde Etmek

Aspirasyon yoluyla Sperm Elde Etmek

Azospermik, nonobstrüktif

hastalarda

TFNA (Testicular Fine Needle Aspiration)

TESA (Testicular Sperm Aspiration)

Azospermik, obstrüktif hastalarda

PESA (Percutaneous epididymal

sperm aspiration)

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Cerrahi yolla Sperm Elde Etmek

Cerrahi yolla Sperm Elde Etmek

TESE (Testicular sperm extraction)

Mikro-TESE

Azospermik, nonobstrüktif

hastalarda

MESA (Microepididymal sperm

aspiration)

Azospermik, obstrüktif hastalarda

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Complications of infertility treatment

Complications of infertility treatment

• Multiple pregnancy

• Ovarian hyperstimulation syndrome (OHSS)

• Bleeding or infection

• Low birth weight

• Birth defects

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Summary-1Summary-1

1. Multiple causes must be considered for infertility diagnosis and treatment. Female and male reproductive anatomy and physiology should be reviewed in order to encompass the large differential diagnosis and the different factors that may contribute to infertility or subfertility.

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Summary-2Summary-2

2. Infertility is defined as one year of unprotected coitus without conception. Infertility may be primary: a woman who has never achieved pregnancy, or secondary: a woman who has achieved pregnancy in the past. Causes of infertility include tubal and pelvic pathology (35%), male problems (35%), ovulatory dysfunctional (15%), unexplained infertility (10%) and unusual problems (10%).

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Summary-3Summary-3

3. Components of an initial infertility workup include a thorough history and physical examination. Laboratory investigations include a semen analysis to assess male causes of infertility, a method to document that ovulatory cycles are occurring and, often, a hysterosalpingogram to rule out tubal disease.

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Summary-4Summary-4

4. Disorders of ovulation include polycystic ovarian syndrome (PCOS), hyperprolactinoma, thyroid dysfunction and hypothalamic causes and may be diagnosed by history, as well as laboratory tests that document the occurrence of ovulatory cycles. Basal body temperature recording, urinary LH testing, endometrial biopsy and luteal phase serum progesterone testing are all tests that may help confirm the presence or absence of ovulation.

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Summary-5Summary-5

5. Dysfunction of the hypothalamic-pituitary-ovarian axis and medical illness, including thyroid disease and pituitary tumors, can cause ovulatory disturbances. Further laboratory workup targeting these problems should be performed when history, examination, and initial laboratory evaluation indicate ovulatory dysfunction. Medication can also cause ovulatory problems.

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Summary-6Summary-6

6. Ovulatory dysfunction may sometimes be treated with correction of medical disease or change of medications. Most often, ovulatory dysfunction is treated empirically with ovulation induction agents such as clomiphene citrate. A thorough understanding of the normal physiology and pathophysiology of the menstrual cycle aids greatly in the understanding of ovulatory dysfunction.

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Summary-7Summary-7

7. Management of tubal disease is often surgical, including lysis of adhesions and removal of tubal obstruction via either laparoscopy or laparotomy, depending on the severity of the disease.

8. Male fertility problems include varicocele, duct obstruction, sperm antibodies, hypogonadism, testicular hyperthermia, drug use and industrial pollutants.

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Adaleti çiğneyen devlet adamlarını cezalandırmayan milletler çökmek zorundadır. Hz. MUHAMMED

Fenalıkların ilki ve en büyüğü,haksızlıkların cezasız kalmasıdır. EFLATUN

Adaletin kuvvetli, kuvvetlilerin de adaletli olmaları gerekir.Blaise PASCAL

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