Infertility He-Feng Huang Women’s Hospital, School of Medicine, Zhejiang University

Where we come from?

Infertility Definition: The inability to achieve pregnancy after regular unprotected intercourse for a period of 1 year. Primary infertility: never conceived within 1 year Secondary infertility: after a previous pregnancy, unable to conceive again within a 1 year period.

Etiology Female factors Male factors Female and male factors

Female Factor Ovulatory disorders Tubal factors Uterine factors Cervical factors Vulval and vaginal factors

Ovulatory disorders Hypothalamic dysfunction Pituitary dysfunction Ovarian factor Others Hypothalamic-pituitary- ovary axis

Hypothalamic dysfunction Psychological factors: Stress, Disturbance, Anorexia derived from mental stimulus Chronic consumptive diseases: Tuberculosis, Severe malnutrition, Anorexia nervosa

Pituitary dysfunction Pituitary tumors: Pituitary adenoma Pituitary lesions: Empty sella syndrome Sheehan’s Syndrome

Ovarian factors PCOS LUFS POF Ovary insensitivity syndrome Congenital abnormality Surgery or X-ray Ovarian endometriosis Ovarian tumor

PCOS Symptom Menses disturbance and infertility hirsutism, acne, obesity ( BMI ≥ 25 ) Diagnosis （ 1 ） irregular menses or anovulation （ 2 ） experimental or clinical hyperandrogenism （ 3 ） polycystic ovarian morphology observed by ultrasound Accord with 2 points of the three. Follow-up for whole life

Others Thyroid disorder Adrenal dysfunction

Tubal factors Inflammation Surgery of ectopic pregnancy Tubal ovarian effusion Ectopic pregnancy Tubal blockage, hydrosalpinx (HSG ）

Tubal ligation Tubal abnormality Tubal factors Tubal ligation Tuberculosis fallopian tube

Increase of tubal factors STD Repeated intro-uterine manipulation Repeated drug abortion

Uterine factors Uterine developmental abnormality Congenital absence of the uterus Uterine malformation Endometrial abnormality Endometrial tuberculosis Asherman syndrome Uterine tumor

Uterine developmental abnormality

Intrauterine adhesions fibroid

Male factors Semen abnormality Oligospremia, Aspermia, Asthenospermia Sperm transport abnormality Endocrine disorders Sexual dysfunction Immunological factors

Male and female factors Psychological factors Subfertility Immunological factors

Classification

Investigation and Diagnosis Male investigation History: general health, medications, lifestyle and reproductive health General examination Specific examination ： abnormality of genitals seminal analysis

Volume ≥ 2.0ml PH 7.2~7.5 Density ≥ 20×10 /ml Count ≥ 40×10 /every ejaculation ≥ 50% sperm progressive motility (grade a+b) or ≥ 25% sperm rapid progressive motility (grade a) Grade a: rapid progressive motility Grade b: slow progressive motility Morphology ≥ 15% Survive rate ≥ 58% WBC ≤ 1× Normal Seminal analysis （ Fourth/Fifth version ） Volume ≥ 1.5ml PH 7.2~7.5 Density ≥ 15×10 /ml Count ≥ 39×10 /every ejaculation ≥ 32% sperm progressive motility (grade a+b) Grade a: rapid progressive motility Grade b: slow progressive motility Morphology ≥ 4% Survive rate ≥ 50% WBC ≤ 1× Fourth versionFifth version

Female Investigation History General examination Specific examination Others

Specific examination Ovarian examination Ovulation monitor Luteal function Ovarian reserve

Ovarian function Ovulation monitor 1 、 Basic body temperature 2 、 Cervical mucus 3 、 Vaginal cytological test 4 、 Ultrasound monitor 5 、 Serum or urinary LH peak 6 、 Serum E 2 and P levels 7 、 Endometrial biopsy 8 、 Laparoscopy

Follicular development and ovulation

Biphasic basal body temperature

monophasic basal body temperature

Low estrogenHigh estrogen

Cervical mucus

Fern crystallization

Proliferative endometriumSecretory endometrium

Luteal function 1 、 BBT 2 、 Endometrial biopsy 3 、 Serum E2 and P levels

Ovarian reserve 1 、 Age 2 、 Antral follicle count (AFC) 3 、 Basic FSH 、 E2 4 、 CC stimulating test 5 、 GnRH-a stimulating test 6 、 AMH 、 Inhibin B

Tubal investigation Hydrotubation Hysterosalpinography (HSG) Laparoscopy Hysterosalpingography by Ultrasound

Hydrotubation

HSG normal figure

Laparoscopy ： methylene blue liquid

Postcoital test Cervical hostility Hysteroscope Laparoscopy

Postcoital test

Cervical hostility Hysteroscope Laparoscopy

Cervical hostility

Postcoital test Cervical hostility Hysteroscope Laparoscopy

Endometriosis （ Endometriosis （ Laparoscopy)

Treatment of infertility 1.Treatment of genitals organic disease 2.Induction of ovulation 3.Luteal support 4. Improvement of cervical mucus 5.Treatment of tubal inflammation 6.ART

1. Genitals organic disease Genital malformations Genital inflammation Uterine Myoma Endometriosis ----Etiology combined treatment: Infection control, Surgery

2.Tubal infertility Fallopian tube obstraction: Fallopian tube glue loose solution operation Salpingostomy Tubo-uterine implantation Tubal anastomosis Fallopian tubes were partial unobstructed: Liquid instillation Physical therapy Traditional Chinese Medicine

3. Asherman syndrome Principle of Management: Separate adhesions Prevention of adhesion recurrence Promote endometrium repair Methods Hysteroscope management of intrauterine adhesion Estrogen promote endometrium regeneration Intrauterine device (IUD)

1.Reproduction-related disease 2.Induction of ovulation 3.Luteal support 4.Improvement of cervical mucus 5.Treatment of tubal inflammation 6.ART

Drugs for ovulation induction CC HMG FSH: u-FSH, FSH-HP, r-FSH HCG GnRH （ LHRH ） GnRH analog ： GnRH agonist GnRH antagonist bromocriptine

The first R-GN （ Gonal- F+Lhadi+Ovidrel=FSH+LH+HCG ） IVFbaby—Sebastian （ ）

1.Reproduction-related disease 2.Induction of ovulation 3.Luteal support 4. Improvement of cervical mucus 5.Treatment of tubal inflammation 6.ART

1.Reproduction-related disease 2.Induction of ovulation 3.Luteal support 4. Improvement of cervical mucus 5.Treatment of tubal inflammation 6.ART

1.Reproduction-related disease 2.Induction of ovulation 3.Luteal support 4. Improvement of cervical mucus 5.Treatment of tubal inflammation 6.ART

1.Reproduction-related disease 2.Induction of ovulation 3.Luteal support 4. Improvement of cervical mucus 5.treatment of tubal inflammation 6.ART

Summary: Infertility-treatment Azoospermia Genetic disease After surgery Assisted Reproductive Technologies (ART) Unexplained Causes Treatment Anovulation Induction of ovulation Tubal factor Tuboplasty Anatomic factor Microsurgery Immunologic Medication or surgery Immune inhibition

ART Assisted Reproductive technology AID or AIH Artificial insemination IVF-ET In vitro fertilization-embryo transfer

AIH or AID AIH (artificial insemination with husband sperm) IUI (Intrauterine insemination ） IVI (Intravaginal insemination) ICI (Intracervical insemination) ITI (Intratubal insemination) IPI (Intraperitoneal insemination) IFI (Intrafollicle insemination) AID (artificial insemination by donor)

IVF-ET Indication Tubal infertility Endometriosis IUI failure Unexplained infertility Immunological infertility Oligospermia

IVF-ET

Other technology derived from IVF Crypreservation of embryos Oocyte donation and embryo donation Surrogate mother GIFT (Gamete intrafallopian transfer) ZIFT (Zygote intrafallopian transfer) ICSI PGD

ICSI (Intracytoplasmic sperm injection)

PGD Preimplantation genetic diagnosis

PGD indication ★ X-linked chromosome disease ★ Chromosome abnormality (number/structure) ★ Monogenic diseases PGS: Preimplantation genetic screen Advanced age History of habitual abortion Failure of IVF for several times

PGD technique Blastomere Biopsy FISH Single cell PCR Interphase nuclear conversion Whole genomic amplification,WGA Comparative genomic hybridization, CGH

PGD

14 三体 正常 14 三体， 13 单体 Robertsonian translocation （ 13q14q ）

X-linked agammaglobulinemia

IVF-ET protocol Patients preparation COH Oocyte retrieval In vitro fertilization Embryo trasfer Luteal support Follow up

Complication of ART OHSS Ectopic pregnancy and abortion Multiple pregnancy － multiple pregnancy reduction

Transvaginal ultrasound-guided selective fetal reduction

In vitro maturation (IVM) Immature oocytes Mature oocytes embryos

Ethic of ART (Chinese government)  The government does not support nor approve the practice of human clones  Forbid performing ART for single woman  Forbid Manufacturing Oocytes  Forbid commercial trial of zygotes and embryos  Forbid multiple pregnancy dominated ART  Forbid gender selected ART without medical indication  Forbid surrogate motherhood

Ethic of ART Challenge the course of natural reproduction Danger of inbreeding Commercial trial of zygotes and embryos Uncertainty of parenthood Risk of oocyte donation Controversy between clone and traditional family formation Clone criminality Challenge of the definition of “human” ART related regulations and laws