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Saturday, February 19, 2022

Procedures for infertility treatment

In vitro fertilization

In Vitro Fertilization is a fertilization process that is applied on the egg that is combined with the body's sperm but outside it as it is made into glass. This process includes many procedures such as monitoring the ovulatory status of the woman and it removes an egg from her ovaries in order to make them fertilized by the sperm in liquid and the process is made in the laboratory. IVF is a kind of reproductive technology that is assisting in treatment on infertility where a fertilized egg is being implanted in the uterus of the surrogate and then the result is a child that is not related genetically to the surrogate. This process is banned in some countries and others regulate it.  (Hansen et al, 2017)

Medications

There are many fertility drugs that are used lonely as basic types of treatment for inducing ovulation. They may fail as therapy to be used solely so then assistance reproductive procedures can be used with them. Examples are in vitro fertilization for producing more eggs.

There are main three types of fertility drugs which are:

•           Medications for Ovarian Stimulation:

There is the Clomiphene that can be Clomid, Serophene, generic. There is also Letrozole  that is referred to as Femara, ]; human menopausal gonadotrophin (hMG) [Humegon, (FSH) [Follistim, Gonal-F, Bravelle]; and luteneizing hormone (LH) [Luveris. (Mayoclinic, 2017)

•           Medications for Oocyte Maturation:

 Human chorionic gonadotropin (hCG) [Profasi, APL, Novarel, Pregnyl  and Ovidrel

The following table shows treatment for infertility based on the patients' cycle using Clomid:

Figure 2                               

•           Medications to Prevent Premature Ovulation:

 GnRh agonists [leuprolide (Lupron, generic), goserelin (Zoladex)]; nafarelin (Synarel), Gn RH antagonists, ), cetrorelix (Cetrotide )]. [ganirelix (Antagon.

Clomiphene

 

 

 

 

 

 

 

 

 

Clomiphene citrate referred to as (Clomid, Serophene, generic) is always used at first and it is mainly prescribed for the women suffering infrequent periods and or suffering long menstrual cycles. This drug is gentler than other potent drugs which are usually used in superovulation as it is based on blocking estrogen and tricking the pituitary through the production of follicle-stimulating hormone as well as the production of luteinizing hormone (LH). This is important in follicle growth and eggs releasing.

Clomiphene that is usually taken orally through the mouth, very inexpensive, and it bears multiple births risk estimated with a percentage of (about 5%, mostly twins) which is a percentage that is lower than its possibility with the usage of other drugs.

The following conditions can make the women have better chances with this drug:

•           Polycystic ovarian syndrome (PCOS

 •          having ability for menstruation but their menstrual cycle is irregular.

While the following conditions can make women have low chances with the drug:

•           Infertility but having normal ovulation

•           Having Low estrogen levels

•           Suffering Premature ovarian failure

The patient takes one or two daily tablets and this continues for five days and it begins after two to five days of the period. After a week of taking the last pill, ovulation occurs. In case that there is no ovulation, the patient should take higher dose in the next cycle. When this system is not effective too, there should be more prolonged treatment and the patient should take additional drugs and medicines as 6 cycles are the limited period suggested for this treatment by doctors. The quality and amount of cervical mucus can be reduced by Clomiphene as this can make the uterine lining thinner. In this case, the patient should take different drugs to retain thickness. This drug has some side effects such as headache, fatigue, weight gain, hot flashes and nausea.

figure 3

Figure 4

Metformin9,12
Polycystic ovary syndrome (PCOS) is a known hormonal condition that makes women produce higher increasing amount of androgens that then leads to irregular, or no ovulation. Metformin has been used for restoring cyclic ovulation and menses in some cases of women who are suffering from PCOS, though it is lowering the higher increasing blood glucose levels. AEs of metformin has within increased gastrointestinal discomfort, and that medication is contraindicated in some specific patients with the renal dysfunction. (Fodina et al, 2016)

Gonadotropins

This drug is another choice instead of Clomiphene or if it is not effective with the patient, Gonadotropins contain many kinds of drugs based on the FSH as a lonely component or on either combination of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). It works in an indirect way to make the ovaries able to produce the multiple follicles.

Gonadotropins are given to the patients through injection and it includes the following components:

•           Human Chorionic Gonadotropins (hCG)

          Human Menopausal Gonadtropins (hMG), that is also referred to as menotropins

•           Follicle Stimulating Hormone (FSH)

•           Gonadotropin-releasing hormone (GnRH) analogs, which include GnRH agonists and GnRH antagonists

Gonadotropin can be natural compounds that are got from the urine or they can be synthetic compounds formed mainly in a laboratory with the help of recombinant DNA.

Human Menopausal Gonadotropin (hMG).

These drugs are also referred to as menotropins. They include different components such as the LH and FSH and all are derived from postmenopausal women urine. It is taken as injections in series after the start of the period with 2-3 days.   The period of giving the injections to patients is about 7 to 12 days. If there is no ovulation, time is extended.

Human Chorionic Gonadotropin (hCG).

 Human chorionic gonadotropin (hCG) resembels LH. It is like the LH surge that urges the follicle for eggs releasing. Natural hCG drugsare repared from pregnant women urine and they include Pregnyl, Profasi, Novarel, and APL.

The only existed genetically modified hCG drug is Ovidrel which has lower side effects as being injected, it is more able for control than the natural drugs. It is usually used after the usage of either hMG or FSH for stimulating the follicles final maturation stages.

Follicle Stimulating Hormone (FSH).

Urofollitropin referred to as (Bravelle, Fertinex) is a form of FSH which is purified, it is deriving from postmenopausal women urine. Follitropin drugs (Gonal-F, Follistim) are considered synthetic versions of FSH. Sometimes these drugs are presented for patients aligning with an hCG drug.

GnRH Analogs (Agonists or Antagonists).

 Gonadotropin-releasing hormone (GnRH) is a type of hormone that is produced in the brain at the hypothalamus. This drug works to stimulate the pituitary gland to make it form LH and FSH. GnRH is based on synthetic drugs which are considered either antagonists or agonists. They have similarities with the natural GnRH but work differently. Although the natural GnRH stimulates both LH and FSH, the analogs  prevent them from surge that happens exactly prior to ovulation. This prevents the releasing eggs prematuraly before they can be harvested for helping the reproductive technologies.

Figure 5

GnRH agonists include leuprolide (Lupron, generic), nafarelin (Synarel), and goserelin (Zoladex).

•           GnRH antagonists include ganarelix (Antagon) and cetrorelix (Cetrotide).

 GnRH antagonists suppress FSH and LH more than GnRH agonists. Perhaps they need fewer injections.

Figure 6

Complications of Superovulation

Multiple Births:

The follicle overproduction may cause enlargement of the ovarian and this raises the multiple births with a percentage of 25%.  

Ovarian Hyperstimulation Syndrome:

The Ovarian Hyperstimulation Syndrome is considered the most serious complication related to superovulation as it is associated with having enlarged ovary and there is not any known cause for this. This then can lead to having dangerous fluid as well as electrolyte imbalances that may cause damage to liver and can cause damage to kidneys. It is also associated with other symptoms such as high pressure of blood, breathe shortness, nausea, vomiting and abnormal bloating which can endanger the life of the patient.

Bleeding and Rupture of Ovarian Cysts.

If the follicles overproduction is not checked, there could be rapture of ovarian cysts and bleeding. This shows that there is a possibility that clomiphene and gonadotropins can raise the breast and ovarian cancer risks. There isn't clear evidence for that but some studies suggest the relationship between the drug and breast cancer. Other studies suggest that it may reduce the risk for cancer in fact.

Other Drugs Used or Under Investigation

Letrozole and Aromatase Inhibitors.

 

Letrozole (AKA Femara)
Chemical Name: 4,4′-((1H-1,2,4-triazol-1-yl)methylene)dibenzonitrile
Molecular Weight: 285.303 g/mol
Formula: C17H11N5
Original Manufacturer: Novartis
Half Life: 2 – 4 days
Detection Time: 2 weeks
Anabolic Rating: N/A
Androgenic Rating: N/A

Aromatase is blocked by the aromatase inhibitors as the aromatase is an enzyme that is mainly responsible for estrogen production in the tissues of the women bodies outside of their ovaries. These drugs can include some main components such as letrozole (Femara) and anastrozole (Arimidex). Inspite of the fact that letrozole is not agreed as an infertility treatment, it is ususally used in theis purpose in the past few years.

Progesterone.

Progesterone is mainly a hormone that the human body produces in the menstrual cycle. They are given to the women who have suffered miscarriages. The miscarriages are signs of deficiency in the progesterone as the drug of it can be presented to the woman after her retrieval of eggs in the period of in vitro fertilization in order to make the uterine lining thicker and help it be more able to be ready for holding the egg in the next implantation.

Tamoxifen.

Tamoxifen (Nolvadex, generic) is a type of drug referred to also as a selective estrogen-receptor modulator (SERM). It is used for treating or preventing diseases like breast cancer in some specific cases of women. It has been examined in fertility treatments for ovulation inducing. Tamoxifen works in a way that resembles the work of clomiphene but it is different as it may lead to more health hazards with the risk for uterine cancer and blood clots. (Jordan et al, 2016)

Glucocorticoids.

Glucocorticoids drugs are steroid hormones mainly used associated with IVF and intracytoplasmic sperm injection (ICSI) for helping them make the uterus lining more responding to the implantation of the egg. Yet there are other reviews made recently that say that glucocorticoids do is not effective in improving the success of pregnancy and its rates and there is no need for using them routinely with assisted reproductive technologies. (Melo et al, 2015)

Figure 7 fertilization and implantation

Lifestyle Changes

There is not a specific diet that women should follow in order to have good levels of fertility but there are some basic lines for a healthy life style that should be followed to avoid infertility based on passive life styles and these are some tips:

  • Keep a reasonable  healthy weight: Women who are not following rules to keep having healthy weight may be overweight or underweight and this makes them at risk for fertility problems, such as having lower opportunities to succeed in fertility procedures.
  • Don't smoke:  Smoking can raise the infertility risk in both males and females so it is good to avoid smoking that is active or passive.
  • Avoid extra exhausting sporting exercise if it hurts the menstrual cycle. Yet it is important to practice some simple and regular exercise such as aerobe or walking.
  • Reduce the usage of caffeine and alcohol.
  • Don't take any unneeded medications. (Nazni, 2014)

The role of pharmacist in dispensing these drugs (advices to the patients)

Patients who suffer infertility can be advised by the pharmacist about their cases through educating them about many channels such as the information found on media channels as TV and the internet. There are different online surveys and consulting services for infertility but the patients shouldn't investigate and deal with these sites all unless they are well known scientifically by a pharmacist, written by a special person or health organization and they have to be evidence based and peer reviewed. They may be misleading and inaccurate if found online in different sites that may not be educational or scientific. Systematic reviews can be effective and useful, they are advised to read them and make use of the information in them. Patients are also advised to consult doctors early as they have to consult doctors if they feel problems in the menstrual period or in being pregnant or even if they are women who are over 35 and still not pregnant. Pregnancy tests are essential to be made by patients regularly. There is a great role for the pharmacist in dispensing these drugs and managing the infertility in patients as he has to put great attention to the relevant details to the treatment regimens of infertility and advises the patients to do so. A pharmacist can also can be a good source for information of infertility patients, he can tell them about the reliable online sites for information and can also educate them and give them the medication counseling in things and issues such as training on techniques for injection and managing any relevant diverse effects. The pharmacist can also provide patients with assistance with financial considerations related to treatment of infertility and tests needed such as copay savings or prior authorization relevant to the different costs of infertility therapy.  (Barnes and Wiemer, 2015).            

Conclusion

In conclusion, infertility is a case of inability to give birth or be pregnant for longer than a year after regular sexual contact. it is important to focus on the important of fertility and discovering infertility and its reasons early as this helps women treat it effectively and avoid many other relevant health problems. There are many signs and symptoms that can tell the patient should ask a doctor about fertility levels and if the patient suffers infertility and what treatment should be applied with each patient such as the older age than 35 or the irregular menstrual cycle. There are many types of infertility and the doctor can decide this via different measurements and testing. There are many associating risk factors for infertility such as age, weight, smoking and others. The patient can receive different types of treatment and medicines based on the needs and the success of the treatment received by the patient. It is necessary to follow a healthy life style in order to avoid infertility that is related to some bad habits such as smoking or taking too much caffeine or alcohol.

 

References

1.    Barnes, M. Wiemer, D. (2015). 'Therapeutic Management of Infertility: A Pharmacist's Perspective.' https://www.uspharmacist.com/ce/therapeutic-management-of-infertility-a

2.    Dag, Z. Dilbaz, B. (2015). ' Impact of obesity on infertility in women.' PMC. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456969/

3.    Ezzell, W. (2016). 'The Impact of Infertility on Women's Mental Health.' http://www.ncmedicaljournal.com/content/77/6/427.full

4.    Fodina, V. Polukarova, S. Vedmedovska, N. (2016). 'VACTERL association after infertility treatment – case report.'http://www.sciedu.ca/journal/index.php/ijdi/article/view/8835/5677

5.    Hansen, P. Cole, J. Null, D. Dikmen, S. Gaddis, K. (2017). 'Evaluation of genetic components in traits related to superovulation, in vitro fertilization, and embryo transfer in Holstein cattle.' http://www.journalofdairyscience.org/article/S0022-0302(17)30073-5/pdf

6.    J. Datta M.J. Palmer C. Tanton L.J. Gibson K.G. Jones W. Macdowall A. GlasierP. Sonnenberg N. Field C.H. Mercer. A.M. Johnson K. Wellings. (2016). ' Prevalence of infertility and help seeking among 15 000 women and men.' Human Reproduction, Volume 31, Issue 9, 1 September 2016, Pages 2108–2118, https://doi.org/10.1093/humrep/dew123

7.    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2503653/

8.    Masoumi, S. Parsa, P. Darvish, N. Mokhtari, S. Yavangi, M. Roshanaei, G. (2015). 'An epidemiologic survey on the causes of infertility in patients referred to infertility center in Fatemieh Hospital in Hamadan.'https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637117/

9.    Mayoclinic, (2017). 'Female Infertility.' https://www.mayoclinic.org/diseases-conditions/female-infertility/diagnosis-treatment/drc-20354313

10. Melo, A. Ferriani, R. Navarro, P. (2015). 'Treatment of infertility in women with polycystic ovary syndrome: approach to clinical practice.' http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322015001100765

11. Nanzi, P. (2014). ' Association of western diet & lifestyle with decreased fertility.' Indian Journal of Medical Research. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4345758/

12. Patel, A. Sharma, P. Narayan, P. Binu, V. Dinesh, N. Pai, P. (2016). 'Prevalence and predictors of infertility-specific stress in women diagnosed with primary infertility: A clinic-based study.' https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4817284/

13. Poulomi BhattacharyaBalkees Abderrahman, and V. Craig Jordan. (2016). ' Tamoxifen Decreases Mortality, but How?' Journal of Clinical Onology. http://ascopubs.org/doi/full/10.1200/JCO.2016.69.1618

14. Rakesh Sharma,1 Kelly R Biedenharn,1 Jennifer M Fedor,1 and Ashok Agarwa. (2014). ' Lifestyle factors and reproductive health: taking control of your fertility.' PMC. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717046/

15. Samiksha Sharma*, Mahaveer P. Khinchi, Natasha Sharma, Dilip Agrawal and M. K. Gupta. (2015). 'Female Infertility: An Overview.' International Journal of Pharmaceutical Sciences and Research. http://ijpsr.com/bft-article/female-infertility-an-overview/?view=fulltext

16. S Shamila and SL Sasikala, (2011). ' Primary Report on the Risk Factors Affecting Female Infertility in South Indian Districts of Tamil Nadu and Kerala.' Indian Journal f Community Medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3104712/

17. WHO. (2017). 'Infertility  Definition and Terminology.' WHO. http://www.who.int/reproductivehealth/topics/infertility/definitions/en/

https://www.merckmanuals.com/professional/gynecology-and-obstetrics/menstrual-abnormalities/polycystic-ovary-syndrome-pcos

Infertility in Female Patients

 

Pathological Condition

Definition

Female infertility refers to women's inability to reproduce through the natural and normal methods. Infertility is not the natural status of a healthy adult creature as in humans, it is a case among women who are unable to be pregnant or unable to carry pregnancy to full term.    

It can also be referred to as a disease that affects the reproductive system of women as it makes it fail in achieving the clinical pregnancy after the regular sexual intercourse which is unprotected.

It is also the inability of a sexuality active couple to achieve pregnancy in the time period of one year as this can be referred to the male' infertility by different clinical interventions or from laboratory evaluations for the semen. (Dag and Dilbaz, 2015)

Epidemiological definition of infertility

It is a case of non-pregnancy for women who are at the reproductive age between 15 and 49 and who are at the risk of being pregnant as they don't use any contraception and report not successful pregnancy for two years period or more. (Dag and Dilbaz, 2015)

Primary and Secondary Infertility

Infertility can be either primary or secondary as the primary infertility is when the woman is unable to give birth to a child or even be pregnant while the secondary infertility refers to the woman who is unable to give a second birth to a child and she had one before this inability but currently she is not able to be pregnant.  (WHO, 2017).

Incidence                      

In a research there was a prevalence of infertility estimated with 12.5% (CI 95% 11.7–13.3) among women and 10.1% (CI 95% 9.2–11.1) among men. Increased prevalence was related to later cohabitation with a partner and higher socio-economic status. The reported prevalence of asking for help was 57.3% (CI 95% 53.6–61.0) among women.

There are relationship factors that can be associated with infertility experience as according to the research, infertility may be highest with women who are older age and those who first got married at age 35 or more. It can also be more prevalent among women who were treated from depression for more than 12 months.  (Datta et al, 2016)   

Symptoms

There are many symptoms that should be clear for infertility such as the woemn's inability for being pregnant and having long menstrual cycle that comes every more than 35 days or having a very short one that comes every 21 days or less. This means that the menstrual cycle is irregular and if it is absent too, this means symptoms of infertility as ovulating here is stopped or having problems. There may also be no signs or symptoms of infertility clear on the patient. (Fodina et al, 2016)

When the patient have to see a doctor

When seeking for help may be based on the patient's age as:

·         Up to age 35, most doctors ask them and advise them to try to be pregnant for at least a year before making testing or receiving treatment.

·         If the patient is between 35 and 40, discuss the patient's concerns and signs with the doctor after six months trials.

·         If the patient is older than 40, the patient's  doctor may want to start testing or treatment currently and on time.

If the woman and her husband are well aware of some infertility problems and ask doctor's advice, the doctor will start testing and treatment. This also occurs when the patient suffers a history of irregular or absent menstrual cycle or other relevant diseases and health problems. (Sharma et al, 2015)

Risk Factors

There is a number of risk factors that are associated with infertility in women such as the following ones:

Age

The older women are, the less fertility they have. At the age of mid-thirties, fertility begins to decline at women and this is due to the less eggs amount produced by their ovaries. Another problem is that with age, the eggs' quality decrease and there is a risk of having chromosomal abnormalities in the eggs. There are also risks of birth defects as well as miscarriage in addition to the probability of having different health problems that may affect fertility of women. 

Weight

The women's fat cells produce usually about 30% of the women estrogen that is supposed to be mainly produced in the woman's ovaries and this means that the male hormones that are produced by the women's bodies by the adrenal glands are turned into estrogen. This means that very high weight levels can lead to infertility as a result of the abnormal balance of hormones. Women who are also underweight can have infertility levels because of having low body fat levels while being overweight can lead to infertility due to the above normal fat level and this also include women who are suffering eating disorders such as bulimia nervosa or anorexia and women who suffer very low calories levels due to very strict diets and having irregular periods resulting from such diets. Strict vegetarian women also may have problems with fertility if they lack the needed nutrients and vitamins.    

Smoking

Smoking can be very harmful on the ovaries of women as they can lead to eggs decrease as many studies confirm that there is bigger possibility for infertility among smoking women rather than non-smokers as the smoke is more liable to reach the menopause earlier than in the non-smoker women.  

Alcohol and Caffeine Usage

Infertility is seen to be highly associated with the excessive usage of alcohol and caffeine.

Environmental Factors

There are many environmental hazards that may passively affect the levels of fertility in women such as the industrial solvents, pesticides and herbicides. These substances include chemicals that can be attracted to the estrogen of women  and affect their fertility as well as in men too. These chemical can affect the hormones passively and disrupt them which leads to infertility.

Stress and Fertility

There are different chemical messengers in the women's brains that are called Neurotransmitters and they work in the hypothalamus gland that has great control on the stress and reproductive hormones and this in turn passively affects fertility and hinder infertility treatment. (Shamila and Sasikala, 2011)

Diagnosis

When women are unable to be pregnant in a period of time that exceeds a year of unprotected sex, they have to consult a doctor who is specialist in fertility as the doctor can make the required fertility tests that are very necessary especially when the women are at the age of 35 and more or if the woman has some risk factors related with the case such as weight problems or smoking for example. The doctor may also make analysis for the men's semen before making the needed tests for the woman. (Patel et al, 2016)

Medical History and Physical Examination

Completing the medical history is a very important step in the infertility work up added to the physical examinations. This includes asking the patient about her history of sexual activities such as its timing, frequency and menstrual history as well as other life activities such as smoking, alcohol usage and consumption of caffeine. The doctor also asks about other medication that is taken by the patient and her emotional health in order to be helpful guides before testing.

Easy Preliminary Steps

Before making any work up related to fertility, there should be some steps to be taken in order to reduce cost and help, they include the following:

           Monitor basal body temperature. This step is very important to decide about the occurrence of ovulation.

           Test the consistency of women cervical mucus.

           urine test for detecting the luteinizing hormone (LH) surges.

Laboratory Tests

There are many laboratory tests that can be made for testing the infertility causes and then to monitor and decide its treatment such as the blood and urine tests for testing levels of hormones and evaluating them. They may include hormonal tests for the reserve of ovarian especially to be made in older women.

Clomiphene Challenge Test

Here the standard fertility drug can be used for testing the ovarian reserve as here the doctor takes measurements for the FSH in the third day of the cycle. This is done by giving the woman oral clomiphene on the fifth day and ninth of the cycle, then the FSH of the women is measured by the doctor on the tenth day. If the FSH levels are high on third or tenth days, this means there is low chance for good results.

Tissue Samples

Tests for Autoimmune Disease.

Examples of possible results can include:

           High follicle-stimulating hormone (FSH), luteinizing hormone (LH) levels and low estrogen levels suggest premature ovarian failure.

           High LH and low FSH may say that there is polycystic ovary syndrome or defect in the luteal phase.

           High FSH and high estrogen levels on the day three of the cycle predict means there are poor success rates in older women who are trying fertility treatments.

           LH surges indicate that there is ovulation.

           Prolactin levels and thyroid function should be measured as such hormones can affect fertility in an indirect way.

Special Considerations for Patients with Cancer

Women who suffer cancer and are under treatment of it and in need for being pregnant have to seek the consultant of a reproductive specialist who can make a discussion with them about their options. There can be a fertility preservation method for providing them with the best chances for success in the fertility such as the embryo cryopreservation as this method depends on harvesting the eggs of women and then making the needed vitro fertilization and after that to freeze the embryos for being used later.  (Waimey et al, 2015)

Causes

There could be many causes for infertility and the following medical conditions can be among them as they are able to damage the fallopian tubes and makes problems with women ovulation as well as causing some hormonal complications for them.

     Pelvic inflammatory disease

     Premature ovarian failure

     Uterine fibroids

     Endometriosis

     Polycystic ovary syndrome

There are many causes for infertility in women that are related to medical conditions such as the following ones:

           Ovulation problems

           Blocked fallopian tubes

           Structural problems in the reproductive system

           Problems with quality of cervical mucus or eggs

Ovulation Problems

Ovulation is the process of releasing the egg and it happens in the time of the menstrual cycle that occurs every month. The most known causes of infertility are the hormones that are involved into ovulation such as the Polycystic Ovarian Syndrome (PCOS) as women who have PCOS are not able to regular ovulation and they suffer menstrual cycles that are absent or frequent.

In PCOS, there are excessive amounts of androgens (male hormones) that are produced by the ovaries, especially the testosterone. Then comes high levels of luteinizing hormone (LH) as a consequence for the high androgen production and also there is low levels of the FSH or the follicle-stimulating hormone. This process prevents the follicles from the production of the mature eggs and this shortage results in swelling fluid by the follicles and forming the cysts. (Agrawal et al, 2014)

https://www.merckmanuals.com/professional/gynecology-and-obstetrics/menstrual-abnormalities/polycystic-ovary-syndrome-pcos

figure 1

Blocked Fallopian Tubes

Sperm can be prevented from fertilization of the egg as it can't reach it when it is blocked in the fallopian tubes and can't travel to the uterus in order to apply the implantation process. There are many conditions when it is blocked there such as the Pelvic Inflammatory Disease which is an infection in the pelvic and the fallopian tubes, Endometriosis. Endometriosis which is a condition where cells which are in line in the uterus growing in other areas outside of the uterus, examples are the ovaries. Uterine or Abnormal Scarring and Uterine Fibroids as they may contain some substances that block the way in the fallopian tubes and sperm can't go reach the eggs.

Other Causes of Female Infertility

There are other possible causes for women infertility such as the following ones:

           Elevated Prolactin Levels:

Prolactin is a type of hormone that is produced into the pituitary gland which is stimulating the development of breast and milk production during the time of with pregnancy. When there are higher levels of that hormone which is referred to as (hyperprolactinemia), ovulation is inhibited.

           Congenital Structural Abnormalities:

Infertility may be caused by Congenital reproductive tract abnormalities as such malformations normally leave its effect on the vagina or the uterus. Women who are born by women who had taken diethylstilbestrol (DES) while they are pregnant are at higher risk of getting problems in uterine or fallopian tube that have relation to infertility. Yet still some women that are already born and having uterine can be pregnant successfully. Some of such problems can be corrected via surgery.

           Cervical Mucus:

 Infertility can also be affected by either low amounts of cervical mucus or bad quality related to cervical mucus. Problems related to cervical mucus can have relation to prior surgeries, certain medication and hormonal imbalances.

           Egg Quality:

The number of women's egg decrease as long as they grow older and this doesn't mean that young women don't have problems with eggs but they may have them too, this can normally be caused by some medical conditions or having impaired ovaries due to some treatments. These treatment may be cancer treatment such as chemotherapy or radiation as they can leave passive effect over the egg development or even damage them.  (Masoumi et al, 2015)

 

 

 

 

 

 

 

 

 

 

 

 

 

Management of the Disease

Treatment

For treating infertility, there are many procedures that should be done at first. It should investigate any other medical condition that may be relevant to the problems of infertility. If this procedures don not stop the infertility problem, there  should be other extra steps such as the following ones:

  • measures of lifestyles: (examples having a healthy weight, stopping smoking, organizing time of the sexual activity considering the ovulation cycle)
  • Drugs to induce ovulation, examples the clomiphene and gonadotrophins usage.
  • Assisted reproductive technologies (ART), examples the vitro fertilization (IVF) (Ezzell, 2016)

State Audit Institution in Muscat and Salalah

 The State Audit Institution in Muscat main mission and business is to protect public funds and ensure compliance with legislations, laws and regulations related to the state owned entities in Oman. It includes different Regulatory and Administrative Bodies such as the following:

Regulatory Authorities - Financial Services

State Audit Institution (SAI) is the supreme audit institution of the sultanate of Oman. The audit body in Oman was established for more than 34 years and it has developed gradually in many forms from being a department before 1970s in the ministry of finance (the Directorate general of finance then) auditing government expenditures, until it developed in 1999 to become an independent government body that has a head who is a minister.

According to royal decree No. 95/1999 issued by his majesty the Sultan of Oman. The elevation of SAI in 1999 to be an independent government body was immense changes to the government audit practice in Oman, with that the new state audit law came to presence.

There are different projects completed by the State Audit Institution such as the following:

1-    Headquarters Building for State Audit Institution - Al Bustan

The project involves constructing an audit institution that is composed of ground floor and 4 additional floors.

2-    Office Directorate General for Administrative & Financial Audit - Al Batinah.

The project includes constructing an office building.

SAI’s mandate:

SAI works by state audit law issued by royal decree No. 55/2000 which declared SAI as an autonomous legal entity that enjoys a financial, administrative and operational independence that carries out post audits of the state public funds in addition to monitoring the performance of entities falling under its jurisdiction.
SAI’s objectives:

SAI’s objectives to protect the state public funds, expose cases of financial irregularities, draw attention to deficiencies in the financial and personnel laws and to evaluate the performance of entities subject to its audit.

State Audit Institution Salalah

The constitution of SAI:

SAI is headed by a President, in the rank of a Minister, a Deputy President, both appointed by a royal decree, they are supported by an Assistant Deputy President, Advisors, Directors General and Directors as specified in royal decree No. 56 2000 issuing SAI’s organizational structure. SAI currently consists of three main wings, audit, administration, and support services.

SAI’s audit jurisdiction:

The entities subject to the audit of State Audit Institution are: All entities making the administrative apparatus of the state, Public authorities and establishments, Pension funds and private bodies which are subsidised by the government, Companies owned by the government by at least 51% of the share capital or to which the government has granted a concession for a public utility or a natural resource.

SAI’s responsibilities:

SAI’s main responsible for conducting financial and regularity audits, performance audit and follow-up of the implementation of the plan, and review of decisions issued in connection with the financial contraventions.

SAI’s audit reports:

The SAI's reports are issued, usually after every audit, to the entity concerned, which is required to respond to the SAI's findings within a period of two months. The results of the SAI's work throughout the year are summarized in an Annual Report, which is submitted by the President of the SAI to His Majesty the Sultan. This report contains a summary of the SAI's audit findings and action taken thereon by auditors, observations on the State Annual Accounts, an evaluation of performance of the audited entities and development projects, observations on the adequacy of financial laws and regulations, records and systems, as well as observations on financial contraventions and the penalties imposed. The SAI's reports are confidential and available only to the addressee.
SAI and the international community:

SAI is a member of the International Organization of Supreme Audit Institutions (INTOSAI) and is also a member of two of INTOSAI's regional working groups; the Arab Organization for Supreme Audit Institutions (ARABOSAI) and the Asian Organization for Supreme Audit Institutions (ASOSAI).

In 1999, SAI was invited to join INTOSAI's standing committee on Information technology audit, SAI has also joined the INTOSAI committee on internal control and the INTOSAI working group on the audit of privatization. 

The Royal Army of Oman

 

The Royal Army of Oman is the basic forces component of the Sultan of Oman's Armed Forces. It was established in 1907 as the Muscat Garrison.  Currently It has a strength of 25,000 person.

There is a great  military history for Oman and it goes back to the seventh century, it shows how strong that military is.  In 1976. In 1990, Sultan Qaboos bin Said al Said gave the army a new name land forces the Royal Army of Oman (RAO).  The RAO usually exercises with the armed forces of neighbor Gulf Cooperation Council nations and other strategic defense partners such as the US and UK. 

Royal Army of Oman is one of the best and most effective and strongest services in Oman. It was formed as Muscat Garrison in 1907. The Army has become an independent service that was recognized as Sultan of Oman Land Forces. His Majesty Sultan Qaboos bin Said, presented the specific color to the Sultan of Oman Land Forces or Royal Oman Land Forces (ROLF). In 1990, his Majesty has issued different orders to change the title to be as it is now : the Royal Army of Oman. The army is the largest service of the different branches that includes 20,000 strength.  The Sultan’s forces at the beginning of the 20th century were ranging from 50 or 60 men who were armed to defend the Sultan against different attacks to a rather large robust military which included engineers, armored cars, a navy and a modern air force by 1975. This force developed greatly after the Sultan Qaboos took over in 1970. To become that current n modern force that is expanded, the Sultan enlisted the help of the British.
The Royal Army of Oman depends on getting modern military equipment from different areas of the world. It co-operates with different world countries to get the latest types of weapons and to train its members to reach the highest international levels of using weapons and other military techniques.

Many efforts have been exerted by the Royal Army of Oman to be at top of different military organizations in the world as there are different training organizations and programs that are cooperated with the organization such as the following ones:

  • National Defence College Bayt al Falaj, Ruwi, Muscat.
  • Military Technical College near Seeb Airport.
  • Sultan Qaboos Military College (KSQA) including the RAO Officer Training School based at Aydem in Dhofar.
  • Sultan Armed Forces Training Regiment.
  • Battle Training Centre –Saiq- Jebel al Akhdha.