Artificial insemination is a popular treatment option for subfertile couples worldwide. Unofficial records state that the first attempts of artificial fertilization occurred in 1455 when King of Castile tried to impregnant his wife. The first recorded attempt at AF occurred in 1770s by John Hunter, who collected leftover semen from intercourse and injected it into women. (Ombelet & Robays, 2008)

Millions of couples who aspire to have children and start a family struggle with infertility. Even at the peak age for child bearing, over 1 of 10 couples will have difficulties obtaining pregnancy. For females the highest probability of easily becoming pregnant is when at the age 20-24, after this age bracket, the likelihood of infertility gradually increases and conversely, the likelihood of becoming pregnant steadily decreases. This is due to female reproductive biology and the hormonal changes that one experiences throughout her lifetime. On average, once females hit age 40 the probably of becoming pregnant falls steeply, it’s still possible but becomes much more difficult. Normally by the age of 50, women are classified as being permanently infertile. This corresponds with menopause when the ovulation stops due to the ovaries permanently ceasing to carry out their reproductive duties. Studies have revealed that the probability of the cause of infertility within a couple being attributed to the male and the female both being approximately 50%. In the past, females were almost always believed to be the cause of infertility but research has shown that in many cases infertility is due to issues with the male’s reproductive ability. Many treatments do exist for couples to overcome infertility and be able to conceive, but the majority of treatments are for females. For males suffering with infertility, few treatments exist (Hull, 1992).

Diagram showing the inverse relationship between age and female fertility

Retrieved from:www.foxriverwatch.com

Many explanations exist for why a female could be struggle with infertility. They can most easily be broken down into 5 categories:

1) Failure to Ovulate

2) Poorly Functioning Fallopian Tubes

3) Endometriosis

4) Behavioural and Environmental Factors

(retrieved from: https://web.stanford.edu.com)

The failure to normally ovulate accounts as the reason of about 30% of infertility cases. Alterations to the intricate and complex female hormonal balance is most often the cause of female loosing or never having the ability to ovulate. Any issue with the hypothalamus-pituitary gland circuit can cause an imbalance in hormones and offset the critical amount and timing of hormones such as LH (luteinizing hormone) and FSH (follicle stimulating hormone). Hormone imbalances can manifest themselves in many ways. One such illness is Polycystic ovary syndrome which is characterized by an excess of LH release from the pituitary gland and the females either having few or no menstrual periods. Any cause of damage to the ovaries and reproductive organs could cause oligomenorrhea (few menstrual periods) or amenorrhea (no menstrual periods). Multiple surgeries to the lower abodominal area risk scarring the ovaries to the point where they no longer carry out their function. There are also some cases where the female can enter menopause prematurely. For whatever reason, the female permanently ceases to have menstrual periods. The main theory for why this occurs is that the female was either born with a lower than average amount of eggs or ran out of them more quickly than predicted (retrieved from: https://web.stanford.edu.com).

Problems with a female's fallopian tubes account for roughly 25% of female infertility cases. Causes of this range from infections, abdominal diseases, previous surgeries, ectopic pregnancies, and congenital defects.

Endometriosis is a reproductive illness characterized by excessive growth of the uterine lining, roughly 5 million women in the US alone are affected by endometriosis, accounting for 5-7% of all females. The endometrium not only grows within the uterus but also around the fallopian tubes and ovaries.

Diagram showing Endometrious of a female genitalia

Retrieved from:www.foxriverwatch.com

Women concerned about keeping their probability of obtaining pregnancy as high as possible should avoid certain behaviours and environmental hazards. Overall, the statement that “a healthy lifestyle leads to the highest chance of fertility” holds true. A woman that has a healthy diet, exercises regularly, is of healthy weight, has a higher probability of being fertile than a woman that has neglected her health or suffers from obesity. Smoking, alcohol abuse, recreational drug abuse, are all other activities that have shown to decrease a females fertility.

Research within the last few decades has revealed much about male infertility and its causes. These causes can most easily be split into three categories: 1) Hormonal Problems, 2) Physical Problems, 3) Psychological and Behavioural Problems

Male anatomy showing infertility problems

Retrieved from: http://passnownow.com

Males also have a very intricate and complex balance of hormones. Any alteration to this balance, such as too much or too little of LH, FSH, or testosterone will have great negative impacts on one’s reproductive development and reproductive abilities often resulting in fertility issues (retrieved from: https://web.stanford.edu.com).

These problems with the male reproductive system could be from birth or from an injury obtained through their normal lifecycle. Common sources of injury could be from surgeries, accidents (ie. workplace, vehicle), and sports. If any one organ in the reproductive pathway is damaged, it will impair sperm production and result in either/or both decreased sperm count or sperm quality. It is imperative that both sperm count and quality be high for conception to occur (retrieved from: https://web.stanford.edu.com).

Even if there are no hormonal or physical problems, a male can still be considered infertile if a psychological or behavioural issue prevents conception. These issues are manifested in phenomena such as Erectile Dysfunction, Premature Ejaculation, and Ejaculatory Incompetence (retrieved from: https://web.stanford.edu.com).

Intracervical insemination (ICI) is a simple and quick procedure where sperm from a donor or partner is put inside the cervix and they swim up the unterus to the fallopian tubes without help. The procedure is done when the female is ovulating, a speculum is used to open the vagina and expose the cervix. The physcian than uses a syringe to propel the sperm through the cervix, a sponge is placed over the cervix to prevent any leakage, and increase the chances of pregnancy, one round of ICI typically costs between $200 and $300 You may be a good candidate for ICI if you and your partner are having trouble conceiving on your own because your partner is unable to ejaculate during intercourse, or if you are a single woman using a sperm donor. ICI is not the best option for couples with fertility issues such as cervical issues or poor sperm quality in the male donor. Success rates associated with ICI are around 10 percent per cycle, but may increase to as high as 30 percent if good sperm samples are used (Chen et al., 2012)

Intratubal insemination (ITI) is less commonly used because it is invasive and is costly. Similar to IUI but sperm sample is deposited directly into one or both fallopian tubes. ITI is thought to be more effective because sperm are placed right where fertilization occurs. The patient can undergo laparoscopic surgery to find the the fallopian tubes within the abdominal cavity. An incision is made in the abdomen and a tiny camera is inserted to locate the fallopian tubes. and then sperm is deposited into the fallopian tubes (Myers, 2012).

The least common form of artificial insemination also known as self insemination. Very similar to natural intercourse, but a male donor or partner with ejaculate into a cup and then deposit it into the females vagina. This procedure is commonly done if the male has trouble ejaculating during intercourse and has healthy sperm (Chen et al., 2012).

They’re a number of benefits associated with artificial insemination. Firstly, it enables both genders: male and female with infertility issues with a possible solution. More importantly, the artificial techniques involved with sperm donor allow the sperm to be checked prior to fertilization. Therefore, this greatly decreases the possibility of a genetic disorder to be transferred to the child. In addition, the artificial insemination techniques allow individuals of the same gender to have children (Myers, 2012).

The total costs associated with artificial insemination can get costly as it involves professionals to carry out the procedures. It’s also important to be aware of the fact that majority of the departments that provide artificial insemination are self-funding. There are costs associated with the initial analysis with patients. Moreover, there’s also the cost of the drug rehabilitation process. Most importantly, there are costs related with the artificial insemination technique (Todd, 2012).

n Vitro Fertilization refers to the process of mixing an individual egg with semen in a test tube to induce spontaneous fertilization. Once fertilized, the egg can be introduced into the mother via several insemination techniques (Institute for Quality and Efficiency in Health Care, 2014). In one case study it was written that a woman of 37 years of age was not able to become pregnant. Her spouse was 40 years of age. There was a number of tests regarding infertility conducted on her which showed nothing wrong. In addition, her spouse had no problems either regarding the amount of sperm levels. They decided to use in vitro fertilization (Voorhis, 2007).

An alternative to IVF is intra-cytoplasmic Sperm Injection (ICSI), the process of inseminating an egg with a single sperm cell via a micropipette. Like IVF, the fertilized egg is inserted back into the mother or surrogate uterus. This technique is most commonly used when sperm has a low quality, which makes it lack adequate motility or morphology. It is also often used when IVF has been performed in the past and has failed multiple times (Institute for Quality and Efficiency in Health Care, 2014).

In comparison to all the techniques affiliated with infertility, it is known that IVF and ICSI are the most efficient. Surprisingly, women that are under the age of 35 have had a 33 percent rate of successful treatments. As well, greater than 90 percent of the women getting IVF or ICSI will be able to become pregnant. This is taking into consideration that there isn’t the existence of other factors preventing the women from conceiving. There have been studies conducted in the United States, which portray the level of achievement of these techniques to decrease from 40 percent to approximately 22 percent. The reason for this decline is the increase in age of women. Basically, women that range from the ages of 38-40 would have a rate of success: 22 percent. Whereas women within the range 41-42 of age would be 12 percent (Todd, 2012).

Furthermore, studies comparing the efficiency of ICSI and IVF have had inconclusive results as they have only examined both treatments in men with healthy sperm. This eliminates the possibility of sperm quality affecting the treatment (Institute for Quality and Efficiency in Health Care, 2014).

There are a number of reasons, which cause complications in regards to fertility. It is well known that the usage of IVF and/or ICSCI has the greatest possibility regarding successful pregnancy (Voorhis, 2007).

One of the most common risks linked to IVF and ICSI is a resulting number of gestations. When there are several embryos being implanted, it increases the likelihood of pregnancy to occur. However, there is also a statistic, which depicts in the year 2003 out of the total pregnancies with IVF being utilized in the United States, there was a the occurrence of twins for 31 percent. In addition, approximately 3 percent were triplets. In some countries they have actually declined the amount of embryos being placed when there is usage of in vitro fertilization or intra-cytoplasmic sperm injection. Thus, this decreases the total amount of numerous gestation occurring (Voorhis, 2007).

Infants that are conceived with the use of assisted reproductive technologies are more likely to be delivered by caesarean section, have lower birth weight, and are more likely to be born before term maturation (Hansen et al., 2002). Additionally, these babies are twice as prone to risk of a major birth defect, as compared to naturally conceived infants (Hansen et al., 2002). The majority of these defects were detected 6 months after birth. Hansen et al. (2002) also suggested there may be an increase in occurrence of major cardiovascular, chromosomal, and musculoskeletal defects in infants conceived with the use of these technologies. The overall risk of incurring major birth defects was 4.5% for babies who were naturally conceived, and 9.4% for babies who were born using IVF (Hansen et al., 2002)

Several factors may contribute to infant defects, including the age of the parents, the underlying causes to the infertility, and the medications used to induce ovulation or maintain fertility. Additionally, the process of freezing and thawing eggs and embryos may also damage or change important mechanisms essential for normal growth (Hansen et al., 2002).

There is a large amount of research currently being performed on artificial fertilization and reproductive techniques that are showing promise to future infertile couples. Two particular new research papers have been published this year that have greatly helped to pave the pathway of conception all the way through to zygote development.

Researchers from the Wellcome Trust Sanger Institute in Britain reported earlier this year that they have identified a protein-receptor complex that is essential for fertilization of an oocyte (Wellcome Trust Sanger Institute, 2014). The complex consists of the IZUMO1 protein on the cell surface of sperm that binds to the folate receptor 4, now known as the JUNO receptor, on the oocyte surface. The study used mouse derived IVF assays and found that this complex is conserved in humans and other mammals. Interestingly, the complex seemed to disappear after initial fertilization of the oocyte, presumably to prevent multiple sperm from binding to receptor (Bianchi, Doe, Goulding & Wright, 2014). Thus, this paper has shown how the initial stages of conceiving an embryo must occur (Wellcome Trust Sanger Institute, 2014).

Researchers were able to create a synthetic version of the PAWP protein, otherwise known as the sperm post acrosomal WW binding protein (Queen’s University, 2014). The study used both mice eggs and human eggs that were donated by infertile women and were further matured in the lab, rendering them useless for current IVF treatments. Instead, these eggs were injected with PAWP transcripts and observed in vitro (Aarabi et al., 2014). The way this protein was seen to work was by binding the WWI domain of a protein substrate in the oocyte cytoplasm. The interactions triggered an intracellular calcium release, which re-activated the oocyte that was halted at metaphase II prior to fertilization. The most interesting section of the study was that when a PAWP- derived competitive inhibitor was introduced along with the PAWP transcripts, the calcium release was blocked (Aarabi et al., 2014). This is exciting because it demonstrates that PAWP is sufficient to develop a zygote following sperm penetration of the oocyte (Queen’s University, 2014).

Therefore, these research papers, amongst many more, are exciting as they show the identity of the proteins that are required to fertilize an egg that will eventually develop into an embryo; a process that can then be replicated in infertile couples.

Artificial fertilization is an effective method for parents who are not able to conceive through natural methods. There are numerous methods including IVF, ICSI, Intravaginal Insemination, Intratubal Insemination, and many more forms in aiding in pregnancy as well as promising research for the near future. While many methods do exist, some are more invasive than others, and the right form of artificial fertilization for each couple must be considered with the aid of a knowledgeable physician, who knows the situation of each case.

Aarabi, M., Balakier, H., Bashar, S., Moskovtsev, S. I., Sutovsky, P., Librach, C. L., & Oko, R. (2014). Sperm-derived WW domain-binding protein, PAWP, elicits calcium oscillations and oocyte activation in humans and mice. The FASEB Journal, 28(10), 4434-4440.

Bianchi, E., Doe, B., Goulding, D., & Wright, G. J. (2014). Juno is the egg Izumo receptor and is essential for mammalian fertilization. Nature.

Chen, X. J., Wu, L. P., Lan, H. L., Zhang, L., & Zhu, Y. M. (2012). Clinical variables affecting the pregnancy rate of intracervical insemination using cryopreserved donor spermatozoa: a retrospective study in China. International journal of fertility & sterility, 6(3), 179.

Hansen, M., Kurinczuk, J.J., Bower, C., & Webb, S. (2002). The risk of major birth defects after intracytoplasmic serum injection and in vitro fertilization. The New England Journal of Medicine, 346(10), 725-730.

Hull, M. G. (1992). Infertility treatment: relative effectiveness of conventional and assisted conception methods. Human Reproduction, 7 (6), 785 – 796.

Institute for Quality and Efficiency in Health Care. (2014, November 7). Sperm analysis parameters as an indication for ICSI instead of IVF: Benefit still unclear.ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2014/11/141107101745.htm

Myers, H. (2012). The Benefits of Artificial Insemination. Retrieved from: http://www.ehow.com/about_5054889_benefits-artificial-insemination.html

Queen's University. (2014, August 11). Fertile discovery: Treating male infertility with synthetic protein. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2014/08/140811125116.htm

Todd, N. (2012). Infertility and In Vitro Fertilization. Retrieved from:

Tung, N. H., Shoyama, Y., Wada, M., & Tanaka, H. (2014). Improved In Vitro Fertilization Ability of Mouse Sperm Caused by the Addition of Licorice Extract to the Preincubation Medium. Open Reproductive Science Journal, 6, 1-7.

Wellcome Trust Sanger Institute. (2014, April 16). Sperm meets egg: Protein essential for fertilization discovered. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2014/04/140416133253.htm