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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
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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
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T1e boring 1ormonal li-eGGG6784)6780 Embriologie #linica si Reproducere
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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$ulation
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S%P#
usully ,/"S,23
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!2 follicles#o$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
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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
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"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 >>>>>>>>>
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Prader Scale evaluation "emale
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Prader Scale ? evaluation "emalePseudo1ermap1roditismul
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!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
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!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
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Since 677; At1ens5 T1e (nternational %lympic
#ommittee 1as introduced mandatory testing o- se in-emale competitions
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