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Female Infertility

Asist. Univ. Dr. Raluca Tulin

Endocrinology/ Embryology Specialist

Profle: Anatomy

Embryology Departament U!" #arol Davila$

%ptional #ourse &ear '() *eneral !edicine#linical Embryology + Assisted ,umanReproduction

Course 2


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(n-ertility15% of couples

• Pregnancy absence a-ter a year o- unprotectedseual intercourse 0 mont1s i- -234 years old5 – Primary no previous pregnancies5

– Secondary t1e couple already 1ad a pregnancy/c1ild5

6784)6780 Embriologie #linica si ReproducereUmana Asistata


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%vogene9a si varsta



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%vogenese

• ong period 3 (U 86)8; 47 years5in >>



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%vulation

• Releasing t1e secondary oocyte -romt1e ovary under , action

• Signs: – #ervical mucus ? volume increase

@


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%varian cycle is F%T Uterine cycle



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• %varian cycle• "ollicular p1ase

• %vulation

• ut1eal p1ase

• Cody temperature

• *onadotropin

1ormons , "S,5

• ,,. Seual E6Progesteron5

• Uterine cycle• !enstruatin

• Proli-erative

• Secretory6784)6780 Embriologie #linica si Reproducere

Umana Asistata


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T1e boring 1ormonal li-eGGG6784)6780 Embriologie #linica si Reproducere

Umana Asistata


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#ouple (n-ertility

(n A-rica (n t1e Sub)Sa1aran area )67)07H o- couples are in-ertile



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Does age matter>

Age Class births/1,000 ♀

15-19 41.6

20-24 102.625-29 115.6

30-34 95.1

35-39 43.8

40-44 8.7

45-54 0.5



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T1e Success o- ('"

• &ounger t1an 34: ;6H ive birt1• Age 34)3I: 34.8H ive birt1

• Age 3);7: 64H ive birt1

• Age ;8);6: 8;.4H ive birt1

• Age ;3: 4.JH ive birt1

• *reater t1an ;3: 6.JH ive birt1



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#auses o- "emale (n-ertility

– Tubal

– Ovulatory

– Cervical

– Other "Obeity #$%&30 or '19( )o*i+,alcohol recreatio+al ru,/



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(nvestigating "emale (n-ertility

• Ovulatio+ ocu)e+ti+, – $eauri+, boy te)erature "hi,h or )ore tha+ 10

ay/ – ro,etero+e ay 21 "&87 ng/ml /

– i+ ay 3( i &15 )%) " lo ovaria+ reerve orearly )e+oaue/

• Tubal actor – yteroali+,o,rahy or tubal er)eability –

aarocoy or erito+eal actor evaluatio+ – yterocoy



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Paraclinically ,istory

• AGE• ,istory menarc1e !# seual 1istory: seual intercourse

-reKuency pelvic pain endometriosis C(RT,S5$ drugs$surgery$ genetic illnesses$ vaccinations$

• Associated pat1ologies t1yroid 1irsutism acne breast

disc1arge) galactorr1oea5$• Paraclinically:

– AMH PR TS, "T; "S, , E6 Testosterone bio available

– Ab anti rubella Ab anti tooplasma

– #1lamydia !ycoplasma Pelvi (nLamatory Disease maMorcause o- tube in-ertility and cervicitis5

– Ab anti sperm cells inter-eres


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,ig1 ris in-ertility groups

• %ver 34 years old

• Early menopause in -amily medical 1istory

• %nly one ovary

• %P#S• Endometriosis

• Feoplasia 1istory c1emot1erapy

radiot1erapy5• (nsuNcient response to ovarian stimulation

• Uterine anomalies



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Uterine tubes are apro87)86 cm long and 1ave 8); mmdiameter.Subdivided in ; segments: interstitial ist1mus ampullain-undibulum



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,ysterosalpingograp1y

• Radiological procedure involving O )rays 5 used -or visuali9ationo- t1e uterine cavity and -allopian tubes . T1e most commonlyindicated suspicion o- @bloced tubes@. Also visuali9es t1e si9eand s1ape o- t1e uterus uterine cavity 5 in in-ertility problems.

• To c1ec t1e success o- t1e tubal ligation procedure

• #ontraindication: – Pregnancy and pelvic in-ections advised to tae prop1ylactic antibiotic

be-ore any ot1er procedure5

• %ptimum time ? be-ore ovulation day 8); o- !#5

• T1roug1 a transvaginal trans cervical cannula usually


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aparoscopy

• Allo


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Ring sterilization



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,ysteroscopy

• ,ysteroscope is transcervical introduced

• (ndications

– Uterine bleeding myomas endometrial

polyps endometrial atrop1y5 – (n-ertility intrauterine synec1iae

submucosal fbroids5

– Uterine mal-ormations



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teri+e oly

:ouble teru



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%+trauteri+e y+echiae

;her)a+


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=+o)etrial Ca.



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Sycle cell Anemia,emolytic Anemia

• AR needs 6 alleles5

• ,ig1 ,bS H

• Under 1ypoia it createsc1ains o- 1emoglobin and

t1ey polymeri9e andcreates bridges t1atde-orm t1e 1ematite

• T) transplantmedular/1idroyurea



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Tay Sac1•

AR

Deat1 o- nervoussystem

• Absence o-,eosamindase A ,e)A5 accumulation o- -at

acids in nervous cell• ,earing loss blindness

lo


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• #1ildren are born normal anddevelop normal in t1e frst 0 mont1s

• !ost o- t1em die by t1e age o- ;)4years old



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#ystic fbrosis

• AR AQects 8/6477 nb #aucasians5 and8/87.777 Asians5$ i-e epectancy 37/;7years 8J07) t1ey lived appro. 0 mont1s5

• ung pancreas reproductive organs loading


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DA& 68 middle o- luteumstage5

• Progesterone !" ng#mlsuggests o$ulation



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S%P#

usully ,/"S,23

6784)6780Embriologie #linica si ReproducereUmana Asistata


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!2 follicles#o$ary %it& 2'mm diameter$arian $olume!" ml



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• Testosterone – "ree 6)3H5CD5

– Poorly connected to albumin CD5

– Strongly connected to S,C*



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• Presence o- -unctional endometrial tissueoutside t1e uterine cavity AF&=,ERE)lungs intestines peritoneal cavity brain5

• 0)87H o-


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• #A)864 use-ul in monitoring treatment responsecorrelates


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• Any suspicious lesion needs1istologic confrmation



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• Treatment is aimed at lo


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• Progesterone antagonists antiprogesteroneeQect5

• !i-epristone RU );0 5 ? strong antiprogestronic and in1ig1 doses antiglucocorticoid $ 64)877 mg / day

• Dana9ol derived 8I)etiniltestosteron5

677mg3/day until it reac1es amenorr1ea ?

in1ibits *nR, production o- gonadotropins anddecreases t1e -reKuency o- pulsations "S, and, and steroidogenesis and in1ibit production o-estrogen and progestin

– #reate an environment o- 1ypercorti9olemia 1yperandrogenic 1ypoestrogenic un-avorableendometriosis . (n1ibits ovulation .



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• Aromates in1ibitors anastro9ol 8mg/day5

• SER! – Raloi-ene

• Agonists *nR, T8/6 3) ore comparedto )3.4 minute endogenous 1ormone5)

suppresses gonadotropins secretionsi.m s.c intranasal5

• EUPR%(DE CUSERE(FE FA"ARE(FEDES%RE(FE *%SERE(FE TR(PT%RE(FE

• (nduce a reversible pseudomenopause t1roug1do


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> =1y dont



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• Androsperms are more resistant toalaline environmentGGG

• =1at is t1e time period -or 1ig1c1ances o- getting a baby boy>



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>>>>>>>>>>>

Patient 6I years

,o< do post>5



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>>>>>>>>>

• Patient 34 years ) 1ig1 bodytemperature -or mostly 67 days

• Dg>>> posible



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Tae 1ome messages8. .



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6. .



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3.



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;. .



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uestions..9999>>



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T1e seualisation o- t1e body

• Defnition: comple morp1o)-unctional andbe1avioural events t1at determine seualdimorp1ism and mae procreation possible

Stages:

A* ' genetical se+ (c&romosomally),

-* ' gonadic se+,

C* ' internal genital se+,

.* ' e+ternal genital se+,E* ' neuro' be&a$ioural se+



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T1e seualisation o- t1e body

A* Genetic se+: V W 63 X) ;0

Y W 63 or 63 y Z) ;0y

-* Gonadic se+ ? end o- mont1 6 v.i.u8. UndiQerentiated gonad stage

6. DiQerentiated gonad stage uniseual

/esticular 0 &istologic mont& 1 $*i*u

$ary ' &istologic mont& $*i*u*



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"emale se

• At birt1 ?8)6 mil primary -oliculles contain primaryoocytes5$

• Puberty: ;77.777 primary -oliculles$

• Adult ? ;77 develop into mature -ollicules containsecondary oocytes5

Ovogenesis oocytes I oocytes II needs both X

chromosomes in the absence of one – follicular atresia(Turner syndrome- associated ith foliculle-genesis!



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(nterseuality

• Seualisation disorder c1aracteri9ed by amismatc1 o- seual c1aracters belonging

to some -emales lie males• TRUE 1ermap1roditism

• MA3E#FEMA3E

P4E5.HE6MAPH6.I/I4M



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TRUE 1ermap1roditism

• T1e simultaneous presence in t1e same gonadsor diQerent *%FADS testicular and ovariantissue ovary testis ovotestis 5

• 'ariable aryotype: ;0OO or mosaicism or ;0O&• DiQerentiation %*( %*E ? variable• %*E ? masculine -eminine ambigue• %*( ? -eminine/proper gonad o- t1e same side

• T1e seuali9ation o- puberty ) usually -emaletype

6784)6780Embriologie #linica si Reproducere

Umana Asistata


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TRUE 1ermap1roditism

• ,ormonal values are variable

• [aryotype ) variable

• D* : %*E ambiguous 1ig1lig1tingt1e gonads o- bot1 types$

• Treatment:

- Etraction o- gonadsd.o a-ter

puberty5- %*E correction

• ,ormone replacement t1erapy6784)6780

Embriologie #linica si ReproducereUmana Asistata

"E!AE


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"E!AEPSEUD%,ER!AP,R%D(T(S!

%%[S lie male but OO• T1e presence o- -emale gonad ovary 5 as one gonad genital tract and male secondary seual c1aracters areambiguous interse 5

• P,! is more common t1an P,! as is o-ten given

adrenogenital #ongenital Syndrome #A, )#ongenitalAdrenal 1yperplasia 5


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#ongenital Adrenal,yperplasia

• Defcit 68)1idroila9a #&P68A c1romosomal0p68.3$ REF corte SR5 defcit o- cortisol andaldosteron


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• (n v.i.u ovaries and %*( uterus -allopian tubes and

vagina 1ig1er 5 develop normally t1oug1t t1e lac o-in1ibited A!, produced by testicular Sertoli cell5 .

• T1e nervous system is aQected in t1e >>>>>>>>>


Umana Asistata


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Umana Asistata

Prader Scale evaluation "emale


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Prader Scale ? evaluation "emalePseudo1ermap1roditismul


Umana Asistata

!AE


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!AEPSEUD%,ER!A"R%D(T(S!

loos lie


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#auses o- P,!

• PS! apears t1roug1 : – gonad embryo destruction be-ore masculinity be-ore

seven . 0)86 v.i.u5

– de-ective biosynt1esis o- testosteronedecit 8I_)1ydroylase/8I67)lyase or !9':'Hydro+ysteroidde&ydrogenase 5

• de-ect -ormation o- di1ydrotestosteronedefcit 4α reductase5 – de-ective receptor -or androgen action s1ape in


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Androgen (nsensivity SyndromeResistance to androgens5

• T1e lac o- androgen receptorsOK88)OK86 gene5

• " variable p1enotypes


Umana Asistata


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Umana Asistata

!AE


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!AEPSEUD%,ER!AP,R%D(T(S!• "emini9ing testicle syndrome !orris 5 ) -ully resistant

to androgen receptor de-ects 5 $

• [aryotype ;0 O&

• "emale p1enotype ) 1airless


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"oan of #rc $ueen li&abeth I 'rs allis )impson


Umana Asistata


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Since 677; At1ens5 T1e (nternational %lympic

#ommittee 1as introduced mandatory testing o- se in-emale competitions


Umana Asistata


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