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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

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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

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

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