ALL INDIA INSTITUTE OF MEDICAL SCIENCES

JODHPUR
COLLEGE OF NURSING

RECENT ADVANCEMENT IN INFERTILITY MANAGEMENT

Submitted to: Submitted by:

Ms. Himanshu Vyas Farheen Khan
Associate Professor M.Sc. Nursing 1st year
College of nursing College of nursing
AIIMS Jodhpur AIIMS Jodhpur

DATE OF SUBMISSION: 10/05/2020

 RECENT ADVANCEMENT IN INFERTILITY MANAGEMENT
DEFINITION:

•Infertility is medically define as the inability to conceive following one year regular sexual
intercourse without contraception or after six month if the women is over age 35.

• “Failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual
intercourse.”… (WHO)

• “Failure to achieve a successful pregnancy after 12 months or more of appropriate timed

unprotected intercourse or therapeutic donor insemination and after 6 months for women over 35
years of age”….ASRM (American Society for Reproductive Medicine )

IT IS TWO TYPES

• It is define as difficulty conceiving for a couple who has never before had a child. Primary
infertility:-

• Describe a couple who is having difficulty conceiving when at least one of the partners has
previously had a baby. Secondary infertility:-

Incidence

• Generally worldwide it is estimated that one in seven couples have problems in conceiving.

• In India most of these cases women is the factor.

• Fertility problems affect one in seven couples in United Kingdom

types

• In primary infertility, pregnancy has never occurred.

• In secondary infertility, one or both members of the couple have previously conceived, but are
unable to conceive again after a full year of time.

CAUSES OF FEMALE INFERTITY:-

Acquired According to the American Society for Reproductive Medicine (ASRM),

•Age

• Smoking,

• Sexually Transmitted Infections, and

• Being Overweight or Underweight can all affect fertility.

In broad sense, acquired factors practically include any factor that is not based on a genetic
mutation, including any intrauterine exposure to toxins during fetal development, which may
present as infertility many years later as an adult

AGE

• A woman's fertility is affected by her age.

• The average age of a girl's first period (menarche) is 12-13 but, in postmenarchal girls, about
80% of the cycles are anovulatory in the first year after menarche, 50% in the third and 10% in
the sixth year. • A woman's fertility peaks in the early and mid 20s, after which it starts to
decline, with this decline being accelerated after age 35.

•Tobacco smoking:-

• Tobacco smoking is harmful to the ovaries.

•Nicotine and other harmful chemicals in cigarettes interfere with the body’s ability to create
estrogen.

• Also, cigarette smoking interferes with folliculogenesis, embryo transport,  endometrial

receptivity, endometrial angiogenesis,  uterine blood flow and the uterine myometrium.

•Sexually transmitted infections

•Sexually transmitted infections are a leading cause of infertility.

•They often display few, if any visible symptoms, with the risk of failing to seek proper
treatment in time to prevent decreased fertility.

Body weight and eating disorders

•12% of all infertility cases are a result of a woman either being underweight or overweight.

• Fat cells produce estrogen, in addition to the primary sex organs.

•Too much body fat causes production of too much estrogen

•And the body begins to react as if it is on birth control, limiting the odds of getting pregnant.

Chemotherapy:-

•Chemotherapy poses a high risk of infertility.

•Chemotherapies with high risk of infertility include procarbazine and other alkylating drugs
such as cyclophosphamide, ifosfamide, busulfan, melphalan, chlorambucil and chlormethine.
 •Drugs with medium risk include doxorubicin and platinum analogs such as cisplatin and
carboplatin.

•Female infertility by chemotherapy appears to be secondary to premature ovarian failure by loss

of primordial follicles.

Other acquired factors:-

Diabetes mellitus

Coeliac disease

Significant liver or kidney disease

Thrombophilia

Cannabis Smoking, such as of marijuana causes disturbances in the endocannabinoid system,

potentially causing infertility.

Radiation, such as in radiation therapy.

Genetic factors:-

There are many genes wherein mutation causes female infertility .Also, there are additional
conditions involving female infertility which are believed to be genetic but where no single gene
has been found to be responsible, notably Mayer-Rokitansky-Küstner- Hauser Syndrome
(MRKH).

Hypothalamic-pituitary factors

•Hypothalamic dysfunction

•Hyperprolactinemia

•Premature menopause

•Menopause

•Luteal dysfunction

•Gonadal dysgenesis (Turner syndrome)

•Ovarian cancer

Tubal (ectopic)/peritoneal factors:-

•Endometriosis
•Pelvic adhesions

•Pelvic inflammatory disease (PID, usually due to chlamydia)

•Tubal occlusion

•Tubal dysfunction

•Previous ectopic pregnancy.

Uterine factors:-

•Uterine malformations

•Uterine fibroids

•Asherman's Syndrome

•Implantation failure without any known primary cause. It results in negative pregnancy test
despite having performed e.g. embryo transfer.

Cervical factors:-

•Cervical stenosis

•Antisperm antibodies

•Non-receptive cervical mucus Vaginal factors

•Vaginismus

•Vaginal obstruction

CAUSES OF FEMALE INFERTILITY

There are a number of things that may be keeping away a women from getting pregnant

•Damage to fallopian tubes

•Hormonal problems

•Cervical issues

•Uterine trouble

•"Unexplained" infertility

Tests for Infertility:-

• It includes a blood test to check hormone levels and an endometrial biopsy to examine the
lining of your uterus.

• Hysterosalpingography (HSG)

• Laparoscopy:-

Infertility Treatment:-

•Laparoscopy.:- If patient been diagnosed with tubal or pelvic disease, one option is to get
surgery to reconstruct her reproductive organs. Doctor puts a laparoscope through a cut near her
belly button to get rid of scar tissue, treat endometriosis, open blocked tubes, or remove ovarian
cysts, which are fluid-filled sacs that can form in the ovaries.

•Hysteroscopy :-. In this procedure, the doctor places a hysteroscope into her uterus through her
cervix. It's used to remove polyps and fibroid tumors, divide scar tissue, and open up blocked
tubes.

Medication:- If client have ovulation problems, doctors may be prescribed drugs such
•Clomiphene citrate (Clomid, Serophene)

•Gonadotropins (such as Gonal-f, Follistim, Humegon and Pregnyl),

•or letrozole.

•Metformin (Glucophage

ART PROCEDURE:-

• Intrauterine insemination

• In vitro fertilization

• Gamete intra-fallopian transfer

• Zygote intra-fallopian transfer

• Intracytoplasmic sperm injection

• Cryopreservation

• Sub zonal insemination

• Microsurgical epididymal sperm- testicular aspiration and biopsy

• Ovum donation

• Surrogacy and post humas reproduction

DEFINITION

•ART includes all fertility treatments in which both eggs and sperm are handled.

• In general, ART procedures involve surgically removing eggs from a woman’s ovaries,
combining them with sperm in the laboratory, and returning them to the woman’s body or
donating them to another woman.

• They do not include treatments in which only sperm are handled (i.e., intrauterine—or artificial
—insemination) or procedures in which a woman takes medicine only to stimulate egg
production without the intention of having eggs retrieved.

1.Intrauterine insemination:

• Intrauterine insemination (IUI) involves a laboratory procedure to separate fast moving sperm
from more sluggish or non- moving sperm.

INDICATION:-

• there is unexplained infertility

• there are ovulation problems

• the male partner experiences impotence or premature ejaculation

• Women do not have any known fertility problems but may not have a male partner and are
trying for a baby using donated sperm.

PROCEDURE:-

• If women use fertility drugs to stimulate ovulation, vaginal ultrasound scans are used to track
the development of eggs.

• As soon as an egg is mature, given a hormone injection to stimulate its release.

• The sperm will be inserted 36–40 hours later. The doctor will first insert a speculum into
vagina, as in a smear test, to keep vaginal walls apart.

• A small catheter (a soft, flexible tube) will then be threaded into womb via cervix. The best-
quality sperm will be selected and inserted through the catheter.

• The whole process only takes a few minutes and is usually painless. Some women may
experience a temporary, menstrual-like cramping.

• Women may want to rest for a short time before going home.

For men:
• Men will be asked to produce a sperm sample on the day the treatment takes place.

• The sperm will be washed to remove the fluid surrounding them and the rapidly moving sperm
will be separated out from the slower sperm.

• The rapidly moving sperm will be placed in a small catheter to be inserted into the womb.

• If men are using donated or frozen sperm, it will be removed from frozen storage, thawed and
prepared in the same way.

2. IN VITRO FERTILIZATION

• Definition:-

• Retrieval of eggs from ovaries

• Addition of sperm in lab dish to make fertilization.

• Transformation to mother uterus.

Indications of invitrofertilization Idiopathic causes:-

• Female causes-

• Problem of fallopian tubes obstruction, or salpingectomy due to ectopic pregnancy, or

hydrosalpinx.

• Endometriosis

• Ovulation problem

• Antibodies that effects both eggs and sperms

MALE CAUSES

• Defects in sperm quantity and or quality.

• In-ability of the sperm to penetrate the cervical mucus.

• No sperm seen in the semen fluid.

procedure:-

• Genetics diagnosis:- Pre-implantation genetics diagnosis to rule out genetic disorders

Steps

First step
• Ovarian follicle

• Transvaginal US

• Blood test

• Seminal fluid

• Fallopian tube

• US scan uterus

• US scan- ovaries

Second step:-

ovulation induction

• Producing many good follicles to be fertilized.

• Short or long protocols: is done daily injection of gonadotropins.

• Regular monitoring by ultrasound scan is done.

• Following the follicular development and adjust the dose of the injection accordingly.

• After reaching certain size, the final maturation of those follicles is done by giving HCG.

Third Step:

Egg Retrieval (oocytes)

PROCEDURE

• Egg retrieval is done 34 to 37 hours post HCG injection.

• This procedure is considered as minor surgery.

• It is done under the general anesthesia, using ultrasound guide.

• It takes 15 to 20 minutes. Not more than two hours are required for the patient to recover.

• Then , the patient can leave the hospital. A needle is used to aspirate all follicles.

• The fluid is passed over to the embryologist, who identifies and separates the eggs

Fourth step:

spermand egg donation

• The eggs are prepared and stripped from the surrounding cells.

• At the same time. Sperm preparation is done using a special media.

• We need from 10,000- 100,000 motile sperm to be put beside each in a special dish, this is
called traditional I.V.F.

• It is different from intracytoplasmic sperm injection (ICSI), in which we need only one sperm
to be injected in the cytoplasm of the egg).

• Which is indicated in case where sperm is present in the testes but the semen fluid does not
contain sperm.

Fifth steps :-

fertilization

• After preparing the sperm, and the eggs are put in the same dish, in cases of failed fertilization
we use ICSI procedure.

Six step:

Blastocyst day 5 embryo

• After 18 hours after the eggs. Called zygotes. Are fertilized.

• They are cultured in special incubators to support division and development.

• In this step. If the couple has a history of certain genetics disease and the gene that is causing
that problem is identified, we may do pre- implantation genetic diagnosis.

• Grading of the embryos is done using specific criteria.

Sevensteps:-

embryotransfer

• The embryos are transferred into the uterus after 2 to 5 days from the date of pickup.

• Depending on the quality and quantity of the embryos. • Using a special embryo transfer
catheter.

• The patient is given drugs to help support the implantation procedure

• There is no need for a lengthy hospital stay after the embryo transfer procedure ( usually one
hour is sufficient).

• Residents of other countries can travel the next day if they wish.
GAMETE INTRA FALLOPIAN TRANSFER

• Gamete intrafallopian transfer (GIFT), GIFT is an assisted reproductive procedure which

involves removing a woman’s eggs, mixing them with sperm, and immediately placing them into
a fallopian tube.

INDICATION:-

• Couples with unexplainable infertility

• Couples who have not had success with IVF

• Couples who have a religious or moral reluctance to use IVF

• Women who have at least one healthy fallopian tube

• Couples in which the husband has a low sperm count or other problems with his sperm

ZYGOTE INTRAFALLOPIAN TRANSFER:-

• ZIFT is an assisted reproductive procedure similar to in vitro fertilization and embryo transfer,
the difference being that the fertilized embryo is transferred into the fallopian tube instead of the
uterus.

Indication:-

• Tubal blockage

• Significant tubal damage

• An anatomic problem with the uterus, such as severe intrauterine adhesions

• Sperm that are not able to penetrate an egg

PROCEDURE

• Consents are signed by all parties.

• The woman is stimulated with medications to develop multiple egg development.

• When the woman's follicles are mature, an aspiration procedure is performed to remove the
eggs from her ovaries. The eggs are then fertilized in the laboratory with her partner's sperm.

• The embryos are cultured in the laboratory for 1 day for ZIFT and 2 days with TET. At that
time, a tubal transfer procedure (surgery with laparoscopy) is done which places the embryos in
the woman's fallopian tubes.

Intracytoplasmic sperm injection (ICSI) –

• The ICSI procedure involves a single sperm carefully injected into the center of an egg using a
microneedle, Then the embryo is transferred to the uterus or Fallopian tube. This method is also
sometimes employed when donor sperm is used.

Indications for ICSI:

• sperm cell agglutinates availability

• azoospermia (in this case sperm cells are taken during testicular biopsy)

• unsatisfactory (absent) fertilization of oocytes during previous IVF (in vitro fertilization)
attempts

ICSI methodology includes the following stages:

• ICSI methodology includes the following stages:

• oocytes preparation

• sperm cells preparation

• sperm cell introduction into oocyte cytoplasm using a glass micro- needle

• ICSI is performed only with matured oocytes

OVARY TRANSPLANTS

• The procedure involves the removal of an ovary which is frozen and placed in storage until
required at a later date. This ovary is then thawed out slowly and transplanted back into the body.

Reasons for an ovary transplant

• Early menopause

• Cancer treatment

• Organ transplants

Ovary transplant procedure

• The ovary is removed via keyhole surgery which reduces recovery time. The ovary is then
frozen until further notice.

• The ovary to be transplanted is thawed out slowly beforehand. The transplant procedure is
performed as open surgery this time and involves reconnecting tiny blood vessels to the ovary.
This enables a steady blood flow to the ovary which is vital for it to function.
• It will take a few months following surgery for the ovary to be fully functional but evidence
suggests that normal hormone production occurs within 5 months or so.

• Another option is to transplant sections of ovarian tissue rather than the complete ovary. Some
women have undergone surgery in which strips of ovarian tissue have been transplanted onto
their defective ovary which then enables it work again. And this has resulted in successful
pregnancies.

• During the surgery, the patient receives a graft of ovarian tissue from the donor that is
transplanted to the same area where the ovaries are.

TESTICULAR SPERM ASPIRATION/EXTRACTION (TESA/E)

• The testicular sperm aspiration/extraction (TESA/E) involves the direct removal of sperm from
the testicles, which can then be used in conjunction with Intracytoplasmic sperm injection (ICSI)

CRYOPRESERVATION

• This is a method of embryos, eggs, and sperm preservation by freezing in liquid nitrogen.

• Cryopreservation can be performed as oocyte cryopreservation before fertilization, or as

embryo cryopreservation after fertilization.

• Embryo cryopreservation conditions:

• embryos are frozen only at zygote stage of 2, 4, and 8 cells and blastocysts

• Sperm receiving, freezing and preservation stages:

• Cryopreservation and eggs preservation

INTRODUCTION OF LONG ACTING HORMONE

• The other recent advances include the introduction of long acting hormone injections which is
effective for a week as opposed to the need for having daily hormone injections administered
which has very much simplified the IVF process.

• Gonadotropin Releasing Hormone (GnRH)

• GnRH stands for Gonadotropin Releasing Hormone, which is a peptide ( a molecule which
consists of a chain of amino acids) released by the hypothalamus. GnRH causes the pituitary
gland to release the gonadotropin hormones, FSH ( follicle stimulating hormone) and LH
( luteinising hormone) .

Administration
• GnRH antagonists are administered by either intramuscular injection (abarelix) or subcutaneous
injection (cetrorelix, degarelix and ganirelix).

• Human Chorionic Gonadotropin (HCG)

• When the ovarian follicles have reached a certain degree of development, induction of final
oocyte maturation is performed, generally by an injection of human chorionic gonadotropin
(HCG).

Assisted reproductive technology:-

DEFINITION

• Although various definitions have been used for ART, the definition used by Centers for
Disease Control and Prevention CDC is based on the 1992 Fertility Clinic Success Rate and
Certification Act that requires CDC to publish the annual ART Success Rates Report. According
to this definition, ART includes all fertility treatments in which both eggs and sperm are handled.
In general, ART procedures involve surgically removing eggs from a woman’s ovaries,
combining them with sperm in the laboratory, and returning them to the woman’s body or
donating them to another woman. They do NOT include treatments in which only sperm are
handled (i.e., intrauterine—or artificial—insemination) or procedures in which a woman takes
medicine only to stimulate egg production without the intention of having eggs retrieved.

SUBZONAL INSEMINATION (SUZI),

• An older technique of m icromanipulation used i n cases of male factor in fertility.

Spermatozoa ar e inserted into the periv itelline space afterbreak hing of the zona pelluci da by
mechanical or che mical means. Also calle d subzonal injection.

MICROSURGICAL EPIDIDYMAL SPERM- TESTICULAR ASPIRATION AND BIOPSY :--

• MESA is a procedure to harvest sperm from the epididymis.

indication

• Congenital Bilateral Absence of the Vas Deferens (CBAVD)

•No vasa can be felt on scrotal exam

Procedure:-

• After open up a little tubule, aspirate the fluid and will place it into a special tube to send to the
IVF group for processing and freezing into multiple vials. Usually, this is the only procedure the
male partner ever needs

Egg donation
• is the process by which a woman donates eggs for purposes of assisted reproduction or
biomedical research. For assisted reproduction purposes, egg donation typically involves in vitro
fertilization technology, with the eggs being fertilized in laboratory; more rarely, unfertilized
eggs may be frozen and stored for later use. Egg donation is a third party reproduction as part of
assisted reproductive technology (ART).

Indication:-

• Congenital absence of eggs – Turner syndrome – Gonadal dysgenesis

• Acquired reduced egg quantity – Oophorectomy – Premature menopause – Chemotherapy –

Radiation therapy – Autoimmunity – Advanced maternal age – Compromised ovarian reserve

• Other – Diseases of X-Sex linkage – Repetitive fertilization or pregnancy failure – Ovaries

inaccessible for egg retrieval

Process:-

• The process involves IVF. The resulting offspring will carry genetic material of the donor and
the male partner

• Egg donation process fisrt:-

• Donor and recipient cycles are synchronized.

• Eggs taken from the donor after ovarian stimulation.

• Eggs are fertilized with recipient partner’s sperm.

• Embryos transferred to the uterus of a hormonally primed recipient.

• Egg donation process second:-

• Donor

• Synchronize cycle with recipient

• Ovarian stimulation

• Egg retrieval

• Recipient

• Synchronize cycle with donor

• Preparation of the uterus

• Fertilization
• Embryo transfer

• THE DONAR:-

• Donor recruitment: Who are the donors?

• Donor Screening: How are they tested?

• Donor matching: How do I pick a donor?

• SCREENING:-

• Donors

• Consultation – MD/RN interview

• Psychological testing – Interview – Formal testing

• Blood tests – Infectious disease – Fertility potential: FSH follicle count

Procedure:-

• Egg donors are first recruited, screened, and give consent prior to participation in the IVF
process.

• Once the egg donor is recruited, she undergoes IVF stimulation therapy, followed by the egg
retrieval procedure.

• After retrieval, the ova are fertilized by the sperm of the male partner (or sperm donor) in the
laboratory, and, after several days, the best resulting embryo(s) is/are placed in the uterus of the
recipient, whose uterine lining has been appropriately prepared for embryo transfer before hand.

• The recipient is usually, but not always, the person who requested the service and then will
carry and deliver the pregnancy and keep the baby.

SURROGACY AND POSTHUMAS REPRODUCTION:-

• A surrogacy arrangeme nt or surrogacy agreement is the carrying of a pregnancy for intended

parents

ETHICAL ISSUES

• There are several ethical issues associated with infertility and its treatment.

• High-cost treatments are out of financial reach for some couples.

• Debate over whether health insurance companies (e.g. in the US) should be required to cover
infertility treatment.
• Allocation of medical resources that could be used elsewhere

• The legal status of embryos fertilized in vitro and not transferred in vivo.

• Pro-life opposition to the destruction of embryos not transferred in vivo.

• IVF and other fertility treatments have resulted in an increase in multiple births, provoking
ethical analysis because of the link between multiple pregnancies, premature birth, and a host of
health problems.

• Religious leaders' opinions on fertility treatments.

• Infertility caused by DNA defects on the Y chromosome is passed on from father to son. If
natural selection is the primary error correction mechanism that prevents random mutations on
the Y chromosome, then fertility treatments for men with abnormal sperm (in particular ICSI)
only defer the underlying problem to the next male generation.

LEGAL ASPECTS OF ASSISTED REPRODUCTIVE TECHNOLOGY(ART)

The Indian scenario in this field is quite bleak. Delhi artificial insemination (Human) Act 1995 is
the only statutory act prevailing in India . There is no internal regulatory body like VLA in U.K,
moreover Indian Infertility specialist have rather opposed the steps towards regulation of practice
in this field.

1. Litigation against doctors

a. Not taking proper informed consent

b. Following the birth of a defective child

2. Legitimacy

3. Inheritance of property

4. Consummation of marriage
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