Infertility

InfertilityHe-Feng HuangWomens 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 yearSecondary infertility: after a previous pregnancy, unable to conceive again within a 1 year period.

EtiologyFemale factorsMale factorsFemale and male factors

Female FactorOvulatory disordersTubal factors Uterine factorsCervical factorsVulval and vaginal factors

Ovulatory disordersHypothalamic dysfunctionPituitary dysfunction Ovarian factor OthersHypothalamic-pituitary-ovary axis

Hypothalamic dysfunctionPsychological factors: Stress, Disturbance, Anorexia derived from mental stimulus

Chronic consumptive diseases: Tuberculosis , Severe malnutrition, Anorexia nervosa

Pituitary dysfunction Pituitary tumors: Pituitary adenomaPituitary lesions: Empty sella syndromeSheehans Syndrome

Ovarian factorsPCOSLUFSPOFOvary insensitivity syndrome Congenital abnormalitySurgery or X-rayOvarian endometriosisOvarian tumor

PCOSSymptom Menses disturbance and infertility hirsutism, acne, obesity (BMI 25)Diagnosis1irregular menses or anovulation2experimental or clinical hyperandrogenism3polycystic ovarian morphology observed by ultrasound Accord with 2 points of the three. Follow-up for whole life

OthersThyroid disorder Adrenal dysfunction

Tubal factors

InflammationSurgery of ectopic pregnancy

Tubal ovarian effusion Ectopic pregnancyTubal blockage, hydrosalpinx (HSG

Tubal ligationTubal abnormality

Tubal factorsTubal ligationTuberculosis fallopian tube

Increase of tubal factorsSTDRepeated intro-uterine manipulationRepeated drug abortion

Uterine factorsUterine developmental abnormality Congenital absence of the uterus Uterine malformationEndometrial abnormality Endometrial tuberculosis Asherman syndromeUterine tumor

Uterine developmental abnormality

Intrauterine adhesions fibroid

Male factorsSemen abnormality Oligospremia, Aspermia, Asthenospermia Sperm transport abnormalityEndocrine disordersSexual dysfunction Immunological factors

Male and female factorsPsychological factorsSubfertilityImmunological factors

Classification

Investigation and DiagnosisMale investigationHistory: general health, medications, lifestyle and reproductive healthGeneral examinationSpecific examination abnormality of genitals seminal analysis

Volume 2.0mlPH 7.2~7.5Density 2010 /mlCount 4010 /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 110666Normal Seminal analysisFourth/Fifth versionVolume 1.5mlPH 7.2~7.5Density 1510 /mlCount 3910 /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 110666Fourth versionFifth version

Female InvestigationHistory General examinationSpecific examinationOthers

Specific examinationOvarian examinationOvulation monitor Luteal function Ovarian reserve

Ovarian functionOvulation monitor 1Basic body temperature 2Cervical mucus 3Vaginal cytological test 4Ultrasound monitor 5Serum or urinary LH peak 6Serum E2 and P levels 7Endometrial biopsy 8Laparoscopy

Follicular development and ovulation

Biphasic basal body temperature

monophasic basal body temperature

Low estrogenHigh estrogen

Cervical mucus

Fern crystallization

Proliferative endometriumSecretory endometrium

Luteal function

1BBT 2Endometrial biopsy 3Serum E2 and P levels

Ovarian reserve1Age2Antral follicle count (AFC)3Basic FSHE24CC stimulating test5GnRH-a stimulating test6AMHInhibin B

Tubal investigationHydrotubation Hysterosalpinography (HSG)LaparoscopyHysterosalpingography by Ultrasound

Hydrotubation

HSG normal figure

Laparoscopy methylene blue liquid

Postcoital testCervical hostility Hysteroscope Laparoscopy

Postcoital test

Cervical hostility

EndometriosisLaparoscopy)

Treatment of infertility1.Treatment of genitals organic disease2.Induction of ovulation3.Luteal support4. Improvement of cervical mucus 5.Treatment of tubal inflammation6.ART

1. Genitals organic diseaseGenital malformationsGenital inflammation Uterine MyomaEndometriosis ----Etiology combined treatment: Infection control, Surgery

2.Tubal infertilityFallopian 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 syndromePrinciple of Management: Separate adhesions Prevention of adhesion recurrence Promote endometrium repairMethods Hysteroscope management of intrauterine adhesion Estrogen promote endometrium regeneration Intrauterine device (IUD)

1.Reproduction-related disease2.Induction of ovulation3.Luteal support4.Improvement of cervical mucus 5.Treatment of tubal inflammation6.ART

Drugs for ovulation inductionCCHMGFSH: u-FSH, FSH-HP, r-FSHHCGGnRHLHRHGnRH analogGnRH agonist GnRH antagonistbromocriptine

The first R-GNGonal- F+Lhadi+Ovidrel=FSH+LH+HCGIVFbabySebastian 1997.5.7

1.Reproduction-related disease2.Induction of ovulation3.Luteal support4. Improvement of cervical mucus 5.Treatment of tubal inflammation6.ART

1.Reproduction-related disease2.Induction of ovulation3.Luteal support4. Improvement of cervical mucus 5.treatment of tubal inflammation6.ART

Summary: Infertility-treatmentAzoospermiaGenetic diseaseAfter surgeryAssisted Reproductive Technologies(ART)UnexplainedCausesTreatmentImmunologicMedication or surgeryImmune inhibition

ARTAssisted Reproductive technologyAID or AIH Artificial inseminationIVF-ET In vitro fertilization-embryo transfer

AIH or AIDAIH (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-ETIndicationTubal infertilityEndometriosisIUI failureUnexplained infertilityImmunological infertilityOligospermia

IVF-ET

Other technology derived from IVFCrypreservation of embryosOocyte donation and embryo donationSurrogate motherGIFT (Gamete intrafallopian transfer) ZIFT (Zygote intrafallopian transfer)ICSIPGD

ICSI (Intracytoplasmic sperm injection)

PGDPreimplantation genetic diagnosis

PGD indication X-linked chromosome disease Chromosome abnormality (number/structure) Monogenic diseasesPGS: Preimplantation genetic screenAdvanced ageHistory of habitual abortionFailure of IVF for several times

PGD techniqueBlastomere BiopsyFISHSingle cell PCRInterphase nuclear conversionWhole genomic amplification,WGAComparative genomic hybridization, CGH

141413 Robertsonian translocation 13q14q

X-linked agammaglobulinemia

IVF-ET protocolPatients preparationCOHOocyte retrievalIn vitro fertilizationEmbryo trasferLuteal supportFollow up

Complication of ARTOHSSEctopic pregnancy and abortionMultiple pregnancy multiple pregnancy reduction

Transvaginal ultrasound-guided selective fetal reduction

In vitro maturation (IVM)Immature oocytes Mature oocytesembryos

Ethic of ART (Chinese government)The government does not support nor approve the practice of human clonesForbid performing ART for single womanForbid Manufacturing OocytesForbid commercial trial of zygotes and embryosForbid multiple pregnancy dominated ARTForbid gender selected ART without medical indicationForbid surrogate motherhood

Ethic of ARTChallenge the course of natural reproductionDanger of inbreedingCommercial trial of zygotes and embryosUncertainty of parenthoodRisk of oocyte donationControversy between clone and traditional family formationClone criminalityChallenge of the definition of humanART related regulations and laws

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Infertility