About infertility

About Infertility

Definition

Infertility is defined by the inability to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse 1

 When a woman is unable to ever bear a child, either due to the inability to become pregnant or the inability to carry a pregnancy to a live birth 1

Primary infertility prevalence – 2010 2

    < 1%  < 1% – 1.99%  < 2% – 2.99%  > 3%

When a woman is unable to bear a child, either due to the inability to become pregnant or the inability to carry a pregnancy to a live birth following either a previous pregnancy or a previous ability to carry a pregnancy to a live birth 1

Secondary infertility prevalence – 2010 2

  < 9%   9% – 10.99%     11% – 12.99%  > 13%

Causes

Infertility can be explained by many causes
A distinction is made between female and male infertility
In some cases, it may be combined (causes coming from both woman and man), or unexplained

Infertility can be explained by many causes. A distinction is made between female and male infertility. In some cases, it may be combined (causes coming from both woman and man), or unexplained.

Infertility causes 3
Female
Male
Combined
Unexplained
Others

Female factors

Fallopian tubes abnormalities
Ovulation
Endometriosis
Other causes

Male factors

Sperm count
Sperm morphology
Sperm motility
Other causes

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Infertility causes 3
Female
Male
Combined
Unexplained
Others

Female infertility causes

Fallopian tubes abnormalities
Ovulation factors

Endometriosis
Other causes

Fallopian tubes abnormalities
Ovulation factors
Endometriosis
Other causes

The female reproductive system

Fallopian tubes:
transport sperm towards the egg for fertilization and then fertilized egg to the uterus
Ovary:
secrete estrogen & progesterone; produce eggs
Uterus:
where fœtus develops during pregnancy
Vagina:
where semen enters the body; sperm can then travel up to the uterus and into the Fallopian tubes
Endometrium
Cervix

(a) Fallopian tubes: transport sperm towards the egg for fertilization and then fertilized egg to the uterus

(b) Ovaries: secrete estrogen & progesterone; produce eggs

(c) Uterus: where foetus develops during pregnancy

(d) Vagina: where semen enters the body; sperm can then travel up to the uterus and into the Fallopian tubes

Damaged or blocked Fallopian tubes keep sperm from getting to the egg or block the passage of the fertilized egg into the uterus and may cause woman infertility 4
Functioning and patent (open) Fallopian tubes are necessary for conception (at least one tube) 4

Problems with the regulation of reproductive hormones or problems in the ovary, can cause ovulation disorders and woman infertility 5

Disease in which endometrial-like tissue (glands and stroma) that normally grows inside the uterus grows outside of it and may cause inability to conceive 6
About 30-50% of women with endometriosis present with infertility 6

Other reasons for female infertility include: 7
Uterine or cervical abnormalities (polyps, benign tumors, fibroids, abnormal shape etc.)
Pelvic adhesions
Cancer and its treatment
Autoimmune disorders

Fallopian tube abnormalities

Ovulation

Endometriosis

Other causes

Damaged or blocked Fallopian tubes keep sperm from getting to the egg or block the passage of the fertilized egg into the uterus and may cause woman infertility 4
Functioning and patent (open) Fallopian tubes are necessary for conception (at least one tube) 4

Problems with the regulation of reproductive hormones or problems in the ovary, can cause ovulation disorders and woman infertility 5

Disease in which endometrial-like tissue (glands and stroma) that normally grows inside the uterus grows outside of it and may cause inability to conceive 6
About 30-50% of women with endometriosis present with infertility

Other reasons for female infertility include: 8
Uterine or cervical abnormalities (polyps, benign tumors, fibroids, abnormal shape etc.)
Pelvic adhesions
Cancer and its treatment
Autoimmune disorders

Male infertility causes

Low sperm count (oligospermia)
Abnormal sperm morphology (teratospermia)

Reduced sperm motility (asthenospermia)
Absence of sperm in ejaculate (azoospermia)

As high as 90% of male fertility issues are related to count 8

Sperm count

Sperm morphology

Sperm motility

Unexplained infertility

The diagnosis of unexplained infertility is made after the fertility workup, conducted in both man and woman, and unable to detect any cause 9
Abnormalities are likely present but not detected by current methods

Fertility diagnosis

A couple not able to become pregant after a year of trying will undergo a series of fertility tests 10 – 14

Female fertility workup

To diagnose infertility in women, it is necessary to establish a medical history, perform different general tests, explore ovaries and ovulation, and perform tubal patency test and pelvis and uterine cavity evaluation. Tests may vary from one patient to another, according to patient’s history and profile.

Detailed medical history: medications, illnesses, past surgeries, family health history, occupation, past pregnancies etc.

Medical examination

Sexual history: contraception, sexual intercourse frequency, prior sexual relationships etc.

Viral status (blood tests): HIV*, hepatitis B & C, rubella

Cervical smear test for cancer screening

Chlamydia trachomatis to check for pelvic inflammatory disease

Prolactin & thyroid function (blood tests) for identification of thyroid disorders and/or hyperprolactinemia
*Human immunodeficiency virus

Transvaginal Ultrasound to assess the size and number of follicles

Blood tests to assess hormonal levels: estrogen, progesterone, FSH (Follicle Stimulating Hormone), LH (Luteinising Hormone), AMH (Anti-Mullerian Hormone)

These tests help identifying if there is any Fallopian tube blockage (tubal patency test) or abnormality of the uterus.

Hysterosalpingography (HSG): imaging test during which a dye (oil- or water-based contrast medium) is slowly instilled through the cervix into the uterus and Fallopian tubes, and using fluoroscopy (x-ray equipment)

Sonohysterography: ultrasound procedure during which a fluid is slowly instilled into the uterus and Fallopian tubes through the cervix

Transvaginal ultrasound of the pelvis: examination used to evaluate pelvic pathologies

Hysteroscopy: examination assessing the uterine cavity. A small camera is inserted inside the uterus through the vagina for visualization, with direct transmission onto a screen

Laparoscopy: minimally-invasive surgery where a camera is inserted inside the abdomen through a small incision. The technique helps visualizing the abdominal and pelvic organs

Male fertility workup

To diagnose infertility in men, it is necessary to establish a medical history, perform different general tests and semen analysis

A detailed medical history: medications, illnesses, past surgeries, family health history, occupation, past pregnancies etc.

Medical examination

Sexual history: contraception, sexual intercourse frequency, prior sexual relationships etc.

Viral status (blood tests): HIV*, hepatitis B & C
*Human immunodeficiency virus

The semen analysis is used to evaluate a man’s ejaculated seminal fluid. It determines the sperm count, as well as sperm motility and morphology and therefore men ability to conceive

Fertility treatment options

There are many treatments to help couples become pregnant. The choice of treatment is determined by the infertility cause 11, 12, 15

Life style
changes
Eat healthy diet
Maintain healthy weight
Stop smoking & drinking
Regular
& targeted
unprotected
sexual
intercourse
In specific cases, spontaneous conception may occur
Ovulation
induction
Use of drugs to help ovaries release an egg
Interventional
radiology
Use of imaging guidance for diagnosis
and treatment of Fallopian tubes blockage
(selective salpingography)
Hysteroscopic tubal cannulation
Surgery
Laparoscopy
Tubal surgery
Uterine surgery
Surgical ablation or resection of endometriosis
Intrauterine
Insemination
(IUI)
Healthy sperm is placed inside the uterine cavity as close to the time of ovulation as possible
Assisted
Reproductive
Technology
(ART)
IVF (In Vitro Fertilization)
ICSI (IntraCytoplasmic Sperm Injection)
Life style change
Eat healthy diet
Maintain healthy weight
Stop smoking & drinking
Regular & targeted
unprotected sexual intercourse
In specific cases, spontaneous conception may occur
Ovulation induction
Use of drugs to help ovaries release an egg
Interventional radiology
Use of imaging guidance for diagnosis and treatment of Fallopian tubes blockage (selective salpingography)
Surgery
Laparoscopy
Tubal surgery
Uterine surgery
Surgical ablation or resection of endometriosis
Intrauterine Insemination (IUI)
Healthy sperm is placed inside the uterine cavity as close to the time of ovulation as possible
Assisted Reproductive Technology (ART)
IVF (In Vitro Fertilization)
ICSI (IntraCytoplasmic Sperm Injection)

IUI
(Intra-Uterine Insemination)

During IUI, healthy sperm is placed inside the uterine cavity as close to the time of ovulation as possible 12, 16, 17
Fallopian tubes need to be patent (opened) for IUI

Fertility procedure: Process of IUI

Ovaries are moderately stimulated with fertility drugs to obtain one or two mature follicles

Ovarian response is carefully monitored with transvaginal ultrasonography and hormonal measurements (blood tests)

The ejaculate is collected and the sperms are separated from the seminal fluid using a centrifuge

Sperm is gently injected inside the uterine cavity with the help of a catheter

1. Ovarian stimulation

2 . Ovarian response monitoring

3 . Sperm washing in embryology laboratory

4 . Insemination

Ovaries are moderately stimulated with fertility drugs to obtain one or two mature follicles

Ovarian response is carefully monitored with transvaginal ultrasonography and hormonal measurements (blood tests)

The ejaculate is collected and the sperms are separated from the seminal fluid using a centrifuge

Sperm is gently injected inside the uterine cavity with the help of a catheter

IVF & ICSI
(In Vitro Fertilisation & Intracytoplasmic Sperm Injection)

IVF is an ART procedure that involves extracorporeal fertilization 15, 18, 19
ICSI is a procedure in which a single spermatozoon is injected directly into the woman’s egg 15, 18, 19

Fertility treatment: Process of IVF and ICSI

1 Ovarian stimulation
Ovaries stimulated with fertility drugs to obtain multiple follicles (daily hormonal injections for several days or weeks)
Close monitoring with blood tests and trans-vaginal ultrasound scans
2 Egg collection
Procedure during which eggs are collected from a woman’s ovaries by using an ultrasound guided needle
3a IVF - Insemination & Fertilization
Eggs are left in a small petri dish along with prepared spermatozoa
3b ICSI - Insemination & Fertilization
ICSI takes place in the embryology laboratory: a skilled embryologist (embryo specialist) injects a single sperm into the egg
4 Embryo culture
Embryos are then incubated for a 2-5 days for further development
The best embryos are selected for transfer
5 Embryo transfer to the uterine cavity
Embryo transfer usually takes place on the fifth day after egg collection
6 Cryopreservation of embryos
Any remaining good quality embryo is left for cryopreservation
IVF Insemination
& Fertilization
• Eggs are left in a small petri dish along with prepared spermatozoa
ICSI Insemination
& Fertilization
• ICSI takes place in the embryology laboratory: a skilled embryologist (embryo specialist) will inject a single sperm into the egg
Ovarian
Stimulation
 

• Ovaries stimulated with fertility drugs to obtain multiple follicles (daily hormonal injections for several days or weeks)
• Close monitoring with blood tests and trans-vaginal ultrasound scans

Egg collection
 
• Procedure during which eggs are collected from a woman’s ovaries by using an ultrasound guided needle
Embryo culture
 
 

• Embryos are then incubated for a 2-5 days for further development
• The best embryos are selected for transfer

Embryo transfer
to the uterine
cavity
• Embryo transfer usually takes place on the fifth day after egg collection
Cryopreservation
of embryos
 
• Any remaining good quality embryo is left for cryopreservation

Fertility treatment: success rates

Pregnancy & live birth rates may vary among fertility treatments & patient condition (age, fertility factors etc.) 20

Sucess rate per cycle Pregnancy Live birth
IUI NA Husband: 8.6%
Donor: 11.1%
IVF 29.6% 22.2%
ICSI 27.8% 20.1%

European data 2013

Bibliogaphy

1. WHO. World Health Organization 2018. http://www.who.int/reproductivehealth/topics/infertility/definitions/en/.

2. Mascarenhas MN et al. National, regional, and global trends in infertility prevalence since 1990: a systematic analysis of 277 health surveys. PLoS Med. 2012;9(12):e1001356.

3. Regulated fertility services: a commissioning aid – June 2009, from the Department of Health UK.

4. Kuohung W et al. Causes of female infertility. In: UpToDate, Robert L Barbieri, MD (Ed), 2014.

5. Healy DL et al. Female infertility: causes and treatment. Lancet. 1994 Jun 18;343(8912):1539-44.

6. Bulletti C et al. J Assist Reprod Genet. Endometriosis and infertility. 2010 Aug;27(8):441-7.

7. Mayo Clinic. CON-20198835. March 08, 2018. https://www.mayoclinic.org/diseases-conditions/infertility/symptoms-causes/syc-20354317.

8. Kumar N and Singh AK. Trends of male factor infertility, an important cause of infertility: A review of literature. J Hum Reprod Sci. 2015 Oct-Dec; 8(4): 191–196.

9. Quaas A and Dokras A. Diagnosis and Treatment of Unexplained Infertility. Rev Obstet Gynecol. 2008 Spring; 1(2): 69–76.

10. Practice committee of the American Society for Reproductive Medicine. Diagnostic evaluation of the infertile female: a committee opinion. Vol. 103 No. 6. June 2015.

11. National Collaborating Centre for Women’s and Children’s Health. Fertility: assessment and treatment for people with fertility problems. London, United Kingdom: National Institute for Health and Clinical Excellence (NICE); February 2013:1-63. (Clinical guideline no. 156).

12. ACOG (American Society for Obstetrics & Gynecology. Patients FAQs. FAQ137, October 2017. FAQ175, December 2016. FAQ143, August 2011. FAQ084, October 2011. https://www.acog.org/Patients/FAQs

13. The FIGO Fertility Tool Box™. 2012.

14. Hsu A et al. Invasive and non-invasive methods for the diagnosis of endometriosis. Clin Obstet Gynecol. 2010 Jun; 53(2): 413–419.

15. Zegers-Hochschild F et al. International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary of ART terminology, 2009. Fertil Steril. 2009 Nov;92(5): 1520-4.

16. Cabry-Goubet R et al. Effect of gonadotropin types and indications on homologous intrauterine insemination success: a study from 1251 cycles and a review of the literature. Biomed Res Int. 2017; 2017: 3512784.

17. Kucuk T. Intrauterine insemination: is the timing correct? J Assist Reprod Genet. 2008; 25(8): 427–430.

18. Mohammed K et al. In vitro fertilization. Obstetrics, Gynaecology and Reproductive Medicine. 2013: 23(8); 238-246.

19. Royal College of Nursing (RCN) UK. Performing ultrasound-guided oocyte retrieval. RCN guidance for fertility nurses. 2005.

20. Calhaz-Jorge C et al. European IVF-monitoring Consortium (EIM); European Society of Human Reproduction and Embryology (ESHRE). Hum Reprod. 2017 Oct 1; 32(10): 1957-1973. Assisted reproductive technology in Europe, 2013: results generated from European registers by ESHRE.

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