advances in reproductive endocrinology dr. chris o. aimakhu (mbbs,fwacs,fmcog) consultant...

ADVANCES IN ADVANCES IN REPRODUCTIVE REPRODUCTIVE

ENDOCRINOLOGYENDOCRINOLOGY

DR. CHRIS O. AIMAKHU DR. CHRIS O. AIMAKHU (MBBS,FWACS,FMCOG)(MBBS,FWACS,FMCOG)

CONSULTANT OBSTETRICIAN AND CONSULTANT OBSTETRICIAN AND GYNAECOLOGIST,GYNAECOLOGIST,CATHOLIC HOSPITAL, OLUYORO, IBADAN.CATHOLIC HOSPITAL, OLUYORO, IBADAN.

REPRODUCTIVE REPRODUCTIVE ENDOCRINOLOGYENDOCRINOLOGY

---Provides comprehensive care for a wide range ---Provides comprehensive care for a wide range of reproductive problems.of reproductive problems.

---Common problems evaluated and treated ---Common problems evaluated and treated include:-include:-

Infertility (primary and secondary)Infertility (primary and secondary) Pregnancy lossPregnancy loss General female hormonal disordersGeneral female hormonal disorders Hirsutism (excessive hair growth)Hirsutism (excessive hair growth) Menopausal symptomsMenopausal symptoms EndometriosisEndometriosis

REPRODUCTIVE REPRODUCTIVE ENDOCRINOLOGYENDOCRINOLOGY

Menstrual disorders/problemsMenstrual disorders/problems OsteoporosisOsteoporosis Pelvic painPelvic pain Polycystic Ovarian Syndrome (PCOS)Polycystic Ovarian Syndrome (PCOS) Premenstrual SyndromePremenstrual Syndrome Uterine abnormalitiesUterine abnormalities Sexual dysfunctionSexual dysfunction

WHO IS A REPRODUCTIVE WHO IS A REPRODUCTIVE ENDOCRINOLOGIST?ENDOCRINOLOGIST?

A reproductive endocrinologist is a sub A reproductive endocrinologist is a sub specialist physician who has received specialist physician who has received training (a residency) in Obstetrics and training (a residency) in Obstetrics and Gynaecology, and advanced training (a Gynaecology, and advanced training (a fellowship) in the treatment of fellowship) in the treatment of INFERTILITY, RECURRENT INFERTILITY, RECURRENT MISCARRIAGESMISCARRIAGES and and HORMONAL HORMONAL DISORDERS DISORDERS in women.in women.

WHAT TREATMENT DO WHAT TREATMENT DO REPRODUCTIVE REPRODUCTIVE ENDOCRINOLOGISTS OFFER?ENDOCRINOLOGISTS OFFER?

Reproductive endocrinologist can perform a wide Reproductive endocrinologist can perform a wide variety of treatments for infertility.variety of treatments for infertility.

A variety of fertility tests are run in order to determine A variety of fertility tests are run in order to determine the cause of infertility.the cause of infertility.

Reproductive endocrinologists are trained in Reproductive endocrinologists are trained in advanced advanced procedures procedures that can increase a couples chances of that can increase a couples chances of conceiving such as:conceiving such as:

---Infertility Surgeries,---Infertility Surgeries, ---Procedures to reverse tubal ligation,---Procedures to reverse tubal ligation, ---Use of fertility drugs (e.g. Clomid,Pergonal, Follistim, ---Use of fertility drugs (e.g. Clomid,Pergonal, Follistim,

Repronox) andRepronox) and ---Assisted Reproductive Techniques (ART).---Assisted Reproductive Techniques (ART).

ADVANCES IN REPRODUCTIVE ADVANCES IN REPRODUCTIVE ENDOCRINOLOGYENDOCRINOLOGY

Assisted Reproductive Techniques Assisted Reproductive Techniques (ART).(ART).

Minimal invasive surgeries.Minimal invasive surgeries. Cloning.Cloning. Embryonic stem cells.Embryonic stem cells.

A) ASSISTED REPRODUCTIVE A) ASSISTED REPRODUCTIVE TECHNIQUES (ART)TECHNIQUES (ART)

Any procedure where the Any procedure where the gametegamete is is manipulated or removed from the body manipulated or removed from the body and returned either as an and returned either as an oocyteoocyte or as or as an an embryo.embryo.

The aim is to approximate the The aim is to approximate the eggseggs and and spermssperms at the same time whether within at the same time whether within or outside the body.or outside the body.

A) ASSISTED REPRODUCTIVE A) ASSISTED REPRODUCTIVE TECHNIQUES (ART)(CONTD)TECHNIQUES (ART)(CONTD)

Reproductive technologies have undergone a Reproductive technologies have undergone a rapid evolution from simple procedures like the rapid evolution from simple procedures like the first insemination of fresh donor semenfirst insemination of fresh donor semen almost half a century ago to a position where almost half a century ago to a position where we now have the ability to collect we now have the ability to collect epididymal epididymal spermsperm for micro injection into for micro injection into oocytes;oocytes; freeze, freeze, thaw, and transfer thaw, and transfer donor gametesdonor gametes and and embryos,embryos, create pregnancies in menopausal create pregnancies in menopausal women, and in the near future may be able to women, and in the near future may be able to harvest and store eggs from harvest and store eggs from ovarian biopsies.ovarian biopsies.

INDICATIONS FOR ARTINDICATIONS FOR ART

ART is indicated for the management of ART is indicated for the management of infertility for which conventional care is infertility for which conventional care is INAPPROPRIATEINAPPROPRIATE or has or has FAILED.FAILED.

These include:These include:

---Tubal damage---Tubal damage

---Oligospermia --- < 20 million sperms/ml.---Oligospermia --- < 20 million sperms/ml.

---Azoospermia---Azoospermia

---Unexplained infertility---Unexplained infertility

INDICATIONS FOR INDICATIONS FOR ART(CONTD)ART(CONTD)

***Most recently, ART has made possible the ***Most recently, ART has made possible the Preimplantation diagnosis of genetic diseasePreimplantation diagnosis of genetic disease..

Removal and subsequent chromosomal analysis of a single Removal and subsequent chromosomal analysis of a single blastomere allows, prior to implantation, for the diagnosis of blastomere allows, prior to implantation, for the diagnosis of certain disorders e.g. Homozygous sickle cell disease and certain disorders e.g. Homozygous sickle cell disease and Duchene muscular dystrophy.Duchene muscular dystrophy.

*** It is appropriate that ART is increasingly attracting the attention of *** It is appropriate that ART is increasingly attracting the attention of doctors ,nurses, scientists and the general public,but it must be doctors ,nurses, scientists and the general public,but it must be realized that high-tech ART are only necessary when other realized that high-tech ART are only necessary when other simpler and cheaper measures have been tried without success.simpler and cheaper measures have been tried without success.

*** It is therefore necessary to fully investigate both the male and *** It is therefore necessary to fully investigate both the male and female partners and to take into account all available options.female partners and to take into account all available options.

FACTS ABOUT INFERTILITYFACTS ABOUT INFERTILITY

Accounts for 50% of cases in the Accounts for 50% of cases in the gynaecological clinics in developing gynaecological clinics in developing countries.countries.

Numbers of consultations have risen Numbers of consultations have risen significantly.significantly.

It affects It affects 1 in 10 couples.1 in 10 couples.

DEFINITIONS IN DEFINITIONS IN INFERTILITY INFERTILITY

INFERTILITY –INFERTILITY – Inability of a couple to achieve Inability of a couple to achieve pregnancy (conception) after 12 months (1 year) of pregnancy (conception) after 12 months (1 year) of unprotected regular sexual intercourse (Involuntary unprotected regular sexual intercourse (Involuntary failure to conceive).failure to conceive).

There are 2 types of Infertility:There are 2 types of Infertility: PRIMARY INFERTILITYPRIMARY INFERTILITY - No previous pregnancy. - No previous pregnancy.

SECONDARY INFERTILITYSECONDARY INFERTILITY- Previous pregnancy - Previous pregnancy (irrespective of the outcome).(irrespective of the outcome).

DEFINITIONS IN DEFINITIONS IN INFERTILITY(CONTD)INFERTILITY(CONTD)

INFECUNDABILITYINFECUNDABILITY- Inability of a couple to achieve a live birth - Inability of a couple to achieve a live birth after 12 months of regular unprotected intercourse.after 12 months of regular unprotected intercourse.

VOLUNTARY INFERTILITYVOLUNTARY INFERTILITY- has never tried for a pregnancy and - has never tried for a pregnancy and has taken contraception to avoid pregnancy.has taken contraception to avoid pregnancy.

FERCUNDITYFERCUNDITY- is the capacity to participate in the production of a - is the capacity to participate in the production of a child.child.

FECUNDABILITY-FECUNDABILITY- is the likelihood of pregnancy per month of is the likelihood of pregnancy per month of exposure.exposure.

DEFINITIONS IN DEFINITIONS IN INFERTILITY(CONTD)INFERTILITY(CONTD)

STERILITYSTERILITY- An intrinsic inability to achieve pregnancy. - An intrinsic inability to achieve pregnancy. (Total inability to get pregnant). (Infertility is Relative).(Total inability to get pregnant). (Infertility is Relative).

CHILDLESSNESSCHILDLESSNESS- No child at the end of reproductive life.- No child at the end of reproductive life.

** The chances of conception should be expressed in terms The chances of conception should be expressed in terms of fertility of the couple rather than the individual partner.of fertility of the couple rather than the individual partner.

* Infertility is associated with emotional and social distress.* Infertility is associated with emotional and social distress. * The longer the couple have been trying to conceive * The longer the couple have been trying to conceive

without success, the greater the decline in conception rate.without success, the greater the decline in conception rate.

CONTRIBUTION OF THE CONTRIBUTION OF THE PARTNERS TO INFERTILITYPARTNERS TO INFERTILITY

MaleMale ---- 30% - 40% ---- 30% - 40% FemaleFemale ---- 30% - 40% ---- 30% - 40% Both Both ---- 15% ---- 15% UnexplainedUnexplained ---- 5% -10% ---- 5% -10%

CHANCES OF PREGNANCYCHANCES OF PREGNANCY

60% of couples conceive ----- 6 months. 60% of couples conceive ----- 6 months.

80%-85% conceive ----- 1yr. 80%-85% conceive ----- 1yr. 90% conceive ----2yrs 90% conceive ----2yrs 10-15% ----Infertile10-15% ----Infertile

WHAT IS THE MAGNITUDE WHAT IS THE MAGNITUDE OF INFERTILITY IN NIGERIAOF INFERTILITY IN NIGERIA

It is estimated that 15-20% of couples are It is estimated that 15-20% of couples are facing this problem at any given time.facing this problem at any given time.

In Nigeria, this translates to 2 million In Nigeria, this translates to 2 million couples (i.e. 4 million individuals) that are couples (i.e. 4 million individuals) that are experiencing infertility at any given time.experiencing infertility at any given time.

PROBLEMS OF INFERTILITY IN PROBLEMS OF INFERTILITY IN OUR ENVIROMENTOUR ENVIROMENT

Social Stigma. Social Stigma. Marital instability and social neglect. Marital instability and social neglect. Exploitation and economic deprivation of Exploitation and economic deprivation of

female partners.female partners. Emotional stress / frustration / strained Emotional stress / frustration / strained

relationships/ guilt feelings/ unhappiness and relationships/ guilt feelings/ unhappiness and unfulfilled lives / Psychological unfulfilled lives / Psychological consequences.consequences.

Male ego.Male ego. Divorce.Divorce.

FACTORS CONTRIBUTING TO FACTORS CONTRIBUTING TO THE INCREASED DEMAND OF THE INCREASED DEMAND OF TREATMENTTREATMENT

Increased numbers of women in the Increased numbers of women in the reproductive age group.reproductive age group.

A trend towards a later age of child bearing, A trend towards a later age of child bearing, with more years of exposure to infections or with more years of exposure to infections or toxins as well as age- specific reduction in toxins as well as age- specific reduction in fertility.fertility.

Greater public awareness of the availability Greater public awareness of the availability and scope of such services.and scope of such services.

Availability of new technology and drugs for Availability of new technology and drugs for treatment of previously hopeless cases.treatment of previously hopeless cases.

COMMON CAUSES OF INFERTILITY COMMON CAUSES OF INFERTILITY IN OUR ENVIRONMENTIN OUR ENVIRONMENT

* * Male InfertilityMale Infertility ------ ------Infections ----- GonococcalInfections ----- Gonococcal ------Chlamydia------Chlamydia * * Female InfertilityFemale Infertility -------Tubo – Peritoneal factors-------Tubo – Peritoneal factors (Bilateral blockage/pelvic- (Bilateral blockage/pelvic- adhesions are the commonest)adhesions are the commonest) --------S T I--------S T I --------Post abortal sepsis--------Post abortal sepsis --------Puerperal sepsis--------Puerperal sepsis

WHEN TO INVESTIGATE WHEN TO INVESTIGATE INFERTILE COUPLES INFERTILE COUPLES

When conception does not occur within When conception does not occur within 1 year of unprotected regular coitus.1 year of unprotected regular coitus.

This period could be shortened in This period could be shortened in certain individuals.certain individuals.

It is good to complete investigations It is good to complete investigations within 1 menstrual cycle at least the within 1 menstrual cycle at least the initial evaluation.initial evaluation.

PRINCIPLES OF PRINCIPLES OF MANAGEMENT MANAGEMENT

Deal with the infertile couple together. Deal with the infertile couple together. No one is ‘at fault’ or ‘to blame’ No one is ‘at fault’ or ‘to blame’ Carry out investigations and treatment Carry out investigations and treatment

consistently in proper sequence.consistently in proper sequence.

HISTORICAL HISTORICAL DEVELOPMNTS OF ARTDEVELOPMNTS OF ART

1970s -----Experiments in ovum retrieval IVF + ET.1970s -----Experiments in ovum retrieval IVF + ET.

1978 -----1st IVF – ET baby born at 1978 -----1st IVF – ET baby born at Oldham,Manchester,U.K---- Oldham,Manchester,U.K---- SteptoSteptoe and e and EdwardsEdwards who were the IVF pioneers. who were the IVF pioneers. ((Louise BrownLouise Brown born on 25th July, 1978 and is born on 25th July, 1978 and is presently expecting her first baby which was presently expecting her first baby which was conceived by natural means).conceived by natural means). (The Worlds first (The Worlds first “Test tube baby”“Test tube baby”).).

1983 -----1st Successful human pregnancy following 1983 -----1st Successful human pregnancy following cryopreservation.cryopreservation.

1984 ----- 1st live birth via 1984 ----- 1st live birth via GIFT.GIFT.

HISTORICAL DEVELOPMNTS HISTORICAL DEVELOPMNTS OF ART(CONTD)OF ART(CONTD)

1984 ------ 1st live birth via 1984 ------ 1st live birth via GIFT.GIFT. 1988 ------1st human pregnancy via 1988 ------1st human pregnancy via PZD.PZD. ------1st pregnancy via ------1st pregnancy via SUZI.SUZI. 1992 ----- 1st pregnancy and birth following 1992 ----- 1st pregnancy and birth following

ICSI.ICSI. 1997 till date ----Experimentation and reports 1997 till date ----Experimentation and reports

on on mammalian and human cloning.mammalian and human cloning. 1997 till date ----1997 till date ----Stem cell research.Stem cell research.

TYPES OF ASSISTED TYPES OF ASSISTED REPRODUCTIVE REPRODUCTIVE TECHNIQUESTECHNIQUES

Many procedures and many acronyms which are rapidly Many procedures and many acronyms which are rapidly changing.changing.

Variations of the same standard techniques.Variations of the same standard techniques.1). Timed Intercourse (T.I.)1). Timed Intercourse (T.I.)

2). Intra-Uterine Insemination (IUI)2). Intra-Uterine Insemination (IUI)

3). In - Vitro Fertilization and Embryo Transfer (IVF - ET)3). In - Vitro Fertilization and Embryo Transfer (IVF - ET)

4). Gamete Intra Fallopian Transfer (GIFT)4). Gamete Intra Fallopian Transfer (GIFT)

5). Zygote Intra Fallopian Transfer (ZIFT)5). Zygote Intra Fallopian Transfer (ZIFT)

6).Subzonal Insemination (SUZI)6).Subzonal Insemination (SUZI)

TYPES OF ASSISTED TYPES OF ASSISTED REPRODUCTIVE REPRODUCTIVE TECHNIQUES(CONTD)TECHNIQUES(CONTD)

7). Intra Cytoplasmic Sperm Injection (ICSI)7). Intra Cytoplasmic Sperm Injection (ICSI)8). Direct Oocyte Sperm Transfer (DOST)8). Direct Oocyte Sperm Transfer (DOST)9). Sperm Aspiration Techniques.9). Sperm Aspiration Techniques.

TESA --- Testicular Sperm AspirationTESA --- Testicular Sperm Aspiration PESA --- Percutaneous Sperm AspirationPESA --- Percutaneous Sperm Aspiration MESA --- Micro Epididymal Sperm Aspirations.MESA --- Micro Epididymal Sperm Aspirations.

10). Embryo Freezing.10). Embryo Freezing.11).Third Party ART(Donor Eggs, Donor Sperms 11).Third Party ART(Donor Eggs, Donor Sperms

or Surrogacy).or Surrogacy).

SOME ART PROCEDURESSOME ART PROCEDURES

1).1).TIMED INTERCOURSETIMED INTERCOURSE Medications are administered to promote Medications are administered to promote

ovulation.ovulation. Treatment monitored by ultrasound Treatment monitored by ultrasound

scanning to determine the precise timing scanning to determine the precise timing of the egg release.of the egg release.

The couples are then advised on the best The couples are then advised on the best timing of intercourse.timing of intercourse.

ART PROCEDURES ART PROCEDURES (CONTD)(CONTD)

2). 2). INTRA UTERINE INSEMINATIONINTRA UTERINE INSEMINATION Treatment and monitoring is like in timed Treatment and monitoring is like in timed

intercourse.intercourse. The sperms are specially prepared and The sperms are specially prepared and

introduced into the uterine cavity via a introduced into the uterine cavity via a catheter.catheter.

This can help to overcome cervical This can help to overcome cervical mucus hostility.mucus hostility.


3).3).IN-VITRO FERTILIZATION AND EMBRYO IN-VITRO FERTILIZATION AND EMBRYO TRANSFER (IVF- ETTRANSFER (IVF- ET))

A)---- Unlike the A)---- Unlike the standard ovulation induction regimes,standard ovulation induction regimes, most IVF programs follow the most IVF programs follow the super ovulation regimesuper ovulation regime as this ensures a as this ensures a greater number of harvestable greater number of harvestable eggs.eggs.

---- This consists of an ---- This consists of an initial pituitary down regulation initial pituitary down regulation (desensitization of the pituitary)(desensitization of the pituitary) with a resultant with a resultant complete suppression of ovarian activity.complete suppression of ovarian activity.

Drugs used include the Drugs used include the subcutaneous or intranasal subcutaneous or intranasal GnRH(Gonadotrophin-releasing hormone) GnRH(Gonadotrophin-releasing hormone) analogues(Buserelin,Naferelin,Triptorelin) analogues(Buserelin,Naferelin,Triptorelin) from from DayDay

1 to 141 to 14 of the menstrual cycle. of the menstrual cycle.


This is followed by the This is followed by the standard Human chorionicstandard Human chorionic gonadotrophin (FSH, LH)gonadotrophin (FSH, LH) and and Human menopausal Human menopausal gonadotrophin regime (LH).gonadotrophin regime (LH).

B) -----B) -----HCGHCG is given when there are at least is given when there are at least 3 follicles 17-20 mm3 follicles 17-20 mm in in diameter.diameter.

C) -----C) -----Laparoscopic Laparoscopic or preferably or preferably transvaginal ultrasoundtransvaginal ultrasound guided guided follicular aspirationfollicular aspiration approximately approximately 36 hours36 hours after after HCG HCG injection.injection.

D) -----D) -----Incubation of aspirated eggsIncubation of aspirated eggs (under strict temperature, gas (under strict temperature, gas and aseptic control) for and aseptic control) for 4-6hrs.4-6hrs.This allows This allows development to stage development to stage two metaphase. two metaphase. This is followed by addition of about This is followed by addition of about 200,000 200,000 capacitated sperms per egg.capacitated sperms per egg.


E) ----- E) ----- Regular stereoscopic microscopic evaluation Regular stereoscopic microscopic evaluation is done to determine progress of fertilization etcis done to determine progress of fertilization etc

F) ----- Usually F) ----- Usually after 48 - 72hrs,after 48 - 72hrs, the resultant embryos ( the resultant embryos (2-2-8 cell stage)8 cell stage) are aspirated into a small catheter and are aspirated into a small catheter and transcervically placed in the uterine cavity. Usually transcervically placed in the uterine cavity. Usually twotwo are placed while the remaining may be are placed while the remaining may be cryopreservedcryopreserved for future use or donated.for future use or donated.

G) ----G) ----Luteal supportLuteal support is provided by the administration of is provided by the administration of low dose hCGlow dose hCG or or progesterone.progesterone.


IVF RESULTSIVF RESULTS The realistic pregnancy rate per ET in The realistic pregnancy rate per ET in

IVF is 20-30% overall but this is IVF is 20-30% overall but this is influenced by age and the number of influenced by age and the number of embryos transferred.embryos transferred.

Younger women < 35 years have at least Younger women < 35 years have at least a 33% success rate.a 33% success rate.


COMPLICATIONS OF IVFCOMPLICATIONS OF IVF

i) Multiple pregnanciesi) Multiple pregnancies 1 in 5 IVF pregnancies are multiple if 1 in 5 IVF pregnancies are multiple if

transferring 3 embryos or less.transferring 3 embryos or less. Transferring more than 3 embryos(where Transferring more than 3 embryos(where

available) results in multiple pregnancies available) results in multiple pregnancies in about 40% of IVF babies.in about 40% of IVF babies.


ii) Ovarian hyperstimulation syndrome(OHSS)ii) Ovarian hyperstimulation syndrome(OHSS) Excess response to ovarian stimulants can lead to Excess response to ovarian stimulants can lead to

ovarian enlargement, abdominal distension and pains ovarian enlargement, abdominal distension and pains in up to in up to 7%7% of IVF patients. of IVF patients.

However, serious OHSS involving gross ascites affects However, serious OHSS involving gross ascites affects lessless than 2%than 2% of all patients. of all patients.

The prevention of OHSS is the identification of women The prevention of OHSS is the identification of women at risk (polycystic ovaries, high responders) and either at risk (polycystic ovaries, high responders) and either reduced hMG doses or electively cryopreserving all reduced hMG doses or electively cryopreserving all embryos to avoid pregnancy until the danger has been embryos to avoid pregnancy until the danger has been averted. averted.


iii) Pelvic infectioniii) Pelvic infection Serious infection is rare in IVF.Serious infection is rare in IVF. Prophylactic antibiotics are advised.Prophylactic antibiotics are advised.

iv) Haemorrhageiv) Haemorrhage This can occur during egg collection.This can occur during egg collection. Usually there is a bleeding point, but this stops Usually there is a bleeding point, but this stops

when pressure is applied for a short while.when pressure is applied for a short while.


v) Ectopic pregnancyv) Ectopic pregnancy

vi) Anembryonic pregnancy (Blighted ovum) vi) Anembryonic pregnancy (Blighted ovum)

vii) Spontaneous abortionvii) Spontaneous abortion

viii) Intrauterine growth restriction (IUGR)viii) Intrauterine growth restriction (IUGR)

ix) Preterm deliveryix) Preterm delivery


4).GAMETE INTRAFALLOPIAN TRANSFER (GIFT)4).GAMETE INTRAFALLOPIAN TRANSFER (GIFT) Indicated in patients with at least one normal tube.Indicated in patients with at least one normal tube. Super ovulationSuper ovulation is as above (in IVF-ET) followed by a is as above (in IVF-ET) followed by a

laparoscopic follicular aspiration.laparoscopic follicular aspiration. Capacitated spermsCapacitated sperms and and eggseggs are mixed and placed are mixed and placed

in the catheter.in the catheter. Both are then transferred into the fallopian tubes.Both are then transferred into the fallopian tubes. In this case In this case fertilization occurs naturally within the fertilization occurs naturally within the

body.body. GIFT is not recommended if the fallopian tubes are GIFT is not recommended if the fallopian tubes are

blocked or the sperm quality is far below average. blocked or the sperm quality is far below average.


5). ZYGOTE INTRA FALLOPAIN 5). ZYGOTE INTRA FALLOPAIN TRANSFER (ZIFT)TRANSFER (ZIFT)

Similar to GIFT except that the sperms Similar to GIFT except that the sperms and eggs are incubated first and and eggs are incubated first and transferred after fertilization.transferred after fertilization.


6). INTRA CYTOPLASMIC SPERM INJECTION 6). INTRA CYTOPLASMIC SPERM INJECTION (ICSI)(ICSI)

***Indicated in patients with;***Indicated in patients with; i) Severe oligospermia < 5million/ml,i) Severe oligospermia < 5million/ml, ii) Significant sperm immotility,ii) Significant sperm immotility, iii) Multiple sperm factors,iii) Multiple sperm factors, iv) Failed IVF – ET oriv) Failed IVF – ET or v) Inability of the sperms to penetrate the egg v) Inability of the sperms to penetrate the egg

as confirmed from the as confirmed from the ZONA PELUCIDA ZONA PELUCIDA PENETRATION TEST.PENETRATION TEST.


Steps involved are similar to IVF – ET except Steps involved are similar to IVF – ET except that after aspiration of the eggs, (under an that after aspiration of the eggs, (under an inverted microscope) the eggs and sperm are inverted microscope) the eggs and sperm are held by a system of held by a system of two hyallically - two hyallically - controlled micropipettes.controlled micropipettes.

An egg is held in place by a An egg is held in place by a micropipettemicropipette while another while another micropipettemicropipette picks up a single picks up a single live sperm. The egg cell membrane is then live sperm. The egg cell membrane is then pierced and the pierced and the sperm injected into the sperm injected into the cytoplasm with the resultant fertilization of cytoplasm with the resultant fertilization of the egg.the egg.


7).SPERM ASPIRTION PROCEDURES7).SPERM ASPIRTION PROCEDURES Indicated in severe oligospermia.Indicated in severe oligospermia.This may consist of:This may consist of: I) Testicular Sperm Aspiration (TESA)I) Testicular Sperm Aspiration (TESA) II) Percutaneous Sperm Aspiration II) Percutaneous Sperm Aspiration

(PESA),(PESA), III) Micro Epididymal Sperm Aspiration III) Micro Epididymal Sperm Aspiration

(MESA).(MESA).


8).THIRD PARTY ART8).THIRD PARTY ARTI) Donor SpermsI) Donor Sperms Absence of spermsAbsence of sperms in the man especially due to in the man especially due to

testicular failure has traditionally been treated with testicular failure has traditionally been treated with donor sperms for several decades.donor sperms for several decades.

In these days, it is possible to extract directly from the In these days, it is possible to extract directly from the testes in obstructive azoospermia and the sperms testes in obstructive azoospermia and the sperms directly injected into the eggs.directly injected into the eggs.

Where this procedure of sperm extraction Where this procedure of sperm extraction (PESA/TESA) fails, the only recourse is to use (PESA/TESA) fails, the only recourse is to use donor donor sperms if the couple desires a pregnancy.sperms if the couple desires a pregnancy.


II) Donor eggsII) Donor eggs In In menopausal menopausal or or perimenopausalperimenopausal women desiring pregnancy, women desiring pregnancy,

eggs can be obtained from willing donors (that may be known or eggs can be obtained from willing donors (that may be known or unknown to the recipient), fertilized with the husbands sperms and unknown to the recipient), fertilized with the husbands sperms and the embryos transferred into the uterus of the older woman.the embryos transferred into the uterus of the older woman.

III) SurrogacyIII) Surrogacy Couples desiring their own genetic children, but where the woman Couples desiring their own genetic children, but where the woman

has had a hysterectomy or severe damage to her uterus or has had a hysterectomy or severe damage to her uterus or endometrium, can opt for the use of a surrogate mother’s uterus to endometrium, can opt for the use of a surrogate mother’s uterus to receive embryos generated from the eggs and sperms of the receive embryos generated from the eggs and sperms of the genetic parents. genetic parents.

PRE – CONCEPTION PRE – CONCEPTION DIAGNOSISDIAGNOSIS

SEX SELECTION --- Sex-gene probesSEX SELECTION --- Sex-gene probes have been available for have been available for several years for several years for embryo sexing,embryo sexing, especially where there are especially where there are concerns about concerns about sex linked diseases.sex linked diseases. Social sex selectionSocial sex selection has has ethical implications.ethical implications.

SICKLE CELL DISEASE PREVENTION -SICKLE CELL DISEASE PREVENTION --- -- Embryos selectionEmbryos selection

based on the based on the absence of genetic diseasesabsence of genetic diseases (sickle cell disease is (sickle cell disease is the most common in our environment) is more acceptable in most the most common in our environment) is more acceptable in most cultures or religions than selective pregnancy termination after cultures or religions than selective pregnancy termination after antenatal diagnosis.antenatal diagnosis.

Pre-conception diagnosisPre-conception diagnosis can be applied to just about any can be applied to just about any chromosomal disease, sex-linked disorders or inborn errors of chromosomal disease, sex-linked disorders or inborn errors of metabolism for which appropriate probes have been developed.metabolism for which appropriate probes have been developed.

ISSUES IN ASSISTED ISSUES IN ASSISTED REPRODUCTIONREPRODUCTION

Cost effectivenessCost effectiveness Ethical / moral / legal considerationsEthical / moral / legal considerations Emotional issuesEmotional issues

B)MINIMALLY INVASIVE SURGICAL B)MINIMALLY INVASIVE SURGICAL OPTIONS IN REPRODUCTIVE OPTIONS IN REPRODUCTIVE ENDOCRINOLGYENDOCRINOLGY

Developments of Developments of new surgical techniquesnew surgical techniques and and advances in advances in surgical equipmentssurgical equipments allow us to perform allow us to perform more and more surgical procedures using more and more surgical procedures using LAPAROSCOPY LAPAROSCOPY andand HYSTEROSCOPY. HYSTEROSCOPY.

These novel procedures have revolutionized the These novel procedures have revolutionized the approach to the majority of gynecological disorders.approach to the majority of gynecological disorders.

We can now perform the majority of surgeries without We can now perform the majority of surgeries without the need for the need for larger incisionslarger incisions in the abdominal wall in the abdominal wall and therefore, most often patients can go home on the and therefore, most often patients can go home on the day of surgery and recover to full activity in day of surgery and recover to full activity in approximately two weeks after surgery.approximately two weeks after surgery.

MINIMALLY INVASIVE SURGICAL MINIMALLY INVASIVE SURGICAL OPTIONS IN REPRODUCTIVE OPTIONS IN REPRODUCTIVE ENDOCRINOLGY(CONTD)ENDOCRINOLGY(CONTD)

1) LAPAROSCOPY1) LAPAROSCOPY This refers to the This refers to the transabdominal transabdominal

visualization of the peritoneal cavityvisualization of the peritoneal cavity usually after insuflation with gas.usually after insuflation with gas.

Indications for laparoscopy could be Indications for laparoscopy could be diagnosticdiagnostic or or therapeutic. therapeutic.


Diagnostic Indications for LaparoscopyDiagnostic Indications for LaparoscopyInclude the evaluation of amongst others:Include the evaluation of amongst others: Chronic and acute pelvic pain of indeterminate origin Chronic and acute pelvic pain of indeterminate origin

e.g. endometriosis, acute PID, leaking ectopic e.g. endometriosis, acute PID, leaking ectopic gestation, ovarian cysts/accidentsgestation, ovarian cysts/accidents

Causes of infertilyCauses of infertily Second look evaluation following treatment for cancer Second look evaluation following treatment for cancer

of the ovaryof the ovary Suspected endometriosisSuspected endometriosis Uterine perforationUterine perforation Follicular growth monitoringFollicular growth monitoring


Therapeutic Indications for LaparoscopyTherapeutic Indications for LaparoscopyInclude:Include: Tubal sterilization either by electrical or Tubal sterilization either by electrical or

insertion of bands, rings etcinsertion of bands, rings etc Pelvic adhesiolysisPelvic adhesiolysis Retrieval of lost IUCDsRetrieval of lost IUCDs Aspiration of ovarian cysts including ovarian Aspiration of ovarian cysts including ovarian

cystectomy, wedge resection of the ovary and cystectomy, wedge resection of the ovary and ovarian biopsy.ovarian biopsy.

Laparoscopic myomectomy Laparoscopic myomectomy


MetroplastyMetroplasty Laparoscopic assisted vaginal Laparoscopic assisted vaginal

hysterectomy,LAVHhysterectomy,LAVH Laparoscopic tubal surgery, which may include Laparoscopic tubal surgery, which may include

salpingectomy, salpingostomy, tubal re-salpingectomy, salpingostomy, tubal re-implantationimplantation

Laparoscopic lymphadenectomy, Laparoscopic lymphadenectomy, colposuspensioncolposuspension

As part of the assisted fertilization procedures As part of the assisted fertilization procedures – ova collection, gamete transfer– ova collection, gamete transfer


2) HYSTEROSCOPY2) HYSTEROSCOPY Is the endoscopic evaluation of the uterine cavity using Is the endoscopic evaluation of the uterine cavity using

the Hysteroscope.the Hysteroscope.

The Hysteroscope is very much like an operating The Hysteroscope is very much like an operating Laparoscope with an added channel for the Laparoscope with an added channel for the introduction of fluids used for the distension of the introduction of fluids used for the distension of the uterine cavity.uterine cavity.

Distending media include high molecular weight Distending media include high molecular weight dextran with normal saline,glycine, and 5% dextrose in dextran with normal saline,glycine, and 5% dextrose in water or carbon dioxide.water or carbon dioxide.


With the use of the liquid media, the With the use of the liquid media, the uterine pressure should not exceed uterine pressure should not exceed 150mmHg, and with the use of Co2 the 150mmHg, and with the use of Co2 the flow rate should also not exceed flow rate should also not exceed 100ml/mixture.100ml/mixture.

Hysterosopic evaluations may be Hysterosopic evaluations may be performed either under local or generalperformed either under local or general

aneasthesia.aneasthesia.


Diagnostic and therapeutic indications for Diagnostic and therapeutic indications for HysteroscopyHysteroscopyInclude:Include: Focal biopsy for evaluation of patients with abnormal Focal biopsy for evaluation of patients with abnormal

uterine bleeding.uterine bleeding. Evaluation of patients with infertilityEvaluation of patients with infertility Hysteroscopic endometrial laser coagulation instead of Hysteroscopic endometrial laser coagulation instead of

hysterectomy in patients with endometrial hyperplasia hysterectomy in patients with endometrial hyperplasia or dysfunctional uterine bleedingor dysfunctional uterine bleeding

Hysteroscopic submucous myomectomy or metroplastyHysteroscopic submucous myomectomy or metroplasty Diagnosis and management of Asherman’s syndromeDiagnosis and management of Asherman’s syndrome


Identification and retrieval of lost IUCDs Identification and retrieval of lost IUCDs Excision of polypsExcision of polyps Sterilization Sterilization

C)CLONING C)CLONING

The first mammal cloned from the cell of The first mammal cloned from the cell of an adult, an adult, DOLLY THE SHEEP,DOLLY THE SHEEP,

generated considerable interest generated considerable interest worldwide.worldwide.

It stimulated much discussion about the It stimulated much discussion about the ethics of cloning and also, in particular, ethics of cloning and also, in particular, the potential for human reproductive the potential for human reproductive cloning.cloning.

CLONING(CONTD) CLONING(CONTD)

Dolly was derived from the Dolly was derived from the udderudder( an organ ( an organ shaped like a bag that produces milk shaped like a bag that produces milk and hangs beneath the body)and hangs beneath the body) of a six- of a six-year old year old FINN DORSET EWE FINN DORSET EWE that was cultured that was cultured in the laboratory. The cultured cells were then in the laboratory. The cultured cells were then fused with unfertilized eggs, from which the fused with unfertilized eggs, from which the nuclei had been removed. The variable nuclei had been removed. The variable reconstituted eggs were then implanted into reconstituted eggs were then implanted into the the SURROGATE BLACK EWE. SURROGATE BLACK EWE. One One implanted egg resulted in the birth of implanted egg resulted in the birth of DOLLY.DOLLY.

**** An ewe is a female sheep.**** An ewe is a female sheep.

CLONING(CONTD)CLONING(CONTD)

The production of The production of DOLLY DOLLY demonstrated for demonstrated for the the first timefirst time that a that a NUCLEUSNUCLEUS taken from taken from an an adult celladult cell could be could be REPROGRAMMED REPROGRAMMED to to permitpermit the full rangethe full range of of GENE GENE EXPRESSIONSEXPRESSIONS needed to produce a needed to produce a COMPLETE ANIMAL. COMPLETE ANIMAL.

A clear distinction should be drawn between A clear distinction should be drawn between ‘REPRODUCTIVE CLONING’ ‘REPRODUCTIVE CLONING’ and and ‘THERAPEUTIC’ (NON – REPRODUCTIVE) ‘THERAPEUTIC’ (NON – REPRODUCTIVE) CLONING.CLONING.


REPRODUCTIVE CLONINGREPRODUCTIVE CLONING --- by either --- by either embryo splittingembryo splitting or or nucleus replacement,nucleus replacement, is aimed at birth of is aimed at birth of genetically identical genetically identical individuals.individuals.

****There are ****There are no ethical objectionsno ethical objections to to

genetically identical individuals per se, genetically identical individuals per se,

but there are serious ethical questions but there are serious ethical questions

about instrumentation of human beings.about instrumentation of human beings.


THERAPEUTIC (NON- REPRODUCTIVE) THERAPEUTIC (NON- REPRODUCTIVE) CLONING CLONING --- --- is a term used to describe the is a term used to describe the use of cloning that use of cloning that does not involvedoes not involve the the production of genetically identical individuals, production of genetically identical individuals, has has SCIENTIFIC SCIENTIFIC and and THERAPEUTICTHERAPEUTIC applicationsapplications including including potential therapypotential therapy for for mitochondrial disease and research on mitochondrial disease and research on EMBRYONICEMBRYONIC STEM CELLS,STEM CELLS, which could lead which could lead to the to the development of tissue and possibly development of tissue and possibly organs without the risk of immune organs without the risk of immune rejection.rejection.


****Such cell-based therapies****Such cell-based therapies might be might be used to treat Parkinson’s and used to treat Parkinson’s and Huntington’s disease (nerve cells), Huntington’s disease (nerve cells), muscular dystrophy (striated muscle muscular dystrophy (striated muscle cells) and leukaemia(white blood cells).cells) and leukaemia(white blood cells).

D) EMBYONIC STEM D) EMBYONIC STEM CELLS CELLS

Researchers have been making Researchers have been making embryonic stem embryonic stem cellscells from mice, hamsters and other animals for from mice, hamsters and other animals for several years.several years.

They have been described as the ultimate spare They have been described as the ultimate spare part.part.

Embryonic stem cellsEmbryonic stem cells are found in early stages are found in early stages of the embryo, of the embryo, after theafter the egg is fertilized and has egg is fertilized and has begun dividing,begun dividing, but before the mass of cells attach but before the mass of cells attach itself to the wall of the uterus.itself to the wall of the uterus.

Eventually they Eventually they differentiatedifferentiate into the various cell into the various cell types in the body, and disappear.types in the body, and disappear.

EMBYONIC STEM EMBYONIC STEM CELLS(CONTD)CELLS(CONTD)

Researchers have been able to capture Researchers have been able to capture these cells in their these cells in their undifferentiated stateundifferentiated state and keep them in that state in a culture.and keep them in that state in a culture.

They are presently working on how to They are presently working on how to direct direct these cells to become these cells to become specific types of specific types of cellscells which would allow scientists to which would allow scientists to grow grow an unlimited supply of cells for transplant an unlimited supply of cells for transplant and other aspects of medicine and and other aspects of medicine and biology.biology.

EMBYONIC STEM EMBYONIC STEM CELLS(CONTD)CELLS(CONTD)

Much of the excitement surrounding Much of the excitement surrounding embryonic stem cell research focuses on embryonic stem cell research focuses on their their potential for transplantation to repair potential for transplantation to repair diseased organsdiseased organs. .

With their With their unique ability to differentiate unique ability to differentiate into all cells of the body,into all cells of the body, stem cells may stem cells may be used to treat be used to treat a variety of disorders,a variety of disorders, ranging from diabetes to Parkinson’s ranging from diabetes to Parkinson’s disease and spinal cord injuries.disease and spinal cord injuries.

CONCLUSIONCONCLUSION

The introduction of these The introduction of these advances has provided not only advances has provided not only hope and treatment for the hope and treatment for the infertile couple but also infertile couple but also stimulated continuing research in stimulated continuing research in the field of reproduction.the field of reproduction.

Reproductive advances will make Reproductive advances will make more COUPLES happier.more COUPLES happier.

WOMEN MUST BE HAPPY WOMEN MUST BE HAPPY AND HAVE CHILDRENAND HAVE CHILDREN

THANK YOU

advances in reproductive endocrinology dr. chris o. aimakhu (mbbs,fwacs,fmcog) consultant...

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