Introduction

Infertility is defined as the inability to conceive after a one year period of regular, unprotected sex. For people assigned female at birth (AFAB) over the age of 35, this period is reduced to 6 months due to the reduction in fertility with age. This is because they are born with a limited number of eggs to begin with, but after the age of 35, both the number of eggs and the quality of them drastically reduces. The chances of conception between the ages of 20-34 per menstrual cycle is 25%. After 35, it reduces to 10%, and then to 5% after 40. 

Infertility can be very difficult to navigate for those wanting children. This article will outline the different treatments available for infertility.^1,6

Causes of infertility 

There are a number of reasons why a couple may not be able to conceive. Statistics vary from source to source, but around 50% of couples it is because of female factor infertility. 30% of cases are due to male factor infertility, and the remaining 20% are due to both people in the couple. 

The most common causes of infertility in AFAB people are ovulatory disorders, accounting for 25% of cases. These are essentially problems with the menstrual cycle such as irregular periods, no menstrual periods (amenorrhea) or abnormal bleeding during periods. PCOS (polycystic ovarian syndrome) is a common ovulatory disorder.

The second most common cause of infertility in AFAB people is endometriosis, accounting for 15% of cases. There are various other conditions which may make an AFAB person infertile: untreated sexually transmitted infections (STIs) can impact fertility, having a hysterectomy (for example due to cancer), or hormonal deficiencies. However, some cases of infertility do not have any known cause. This is known as idiopathic infertility.

In AMAB people, the reasons for infertility are either low sperm count (i.e low quantity of sperm) or low quality of sperm (or both). This may or may not have a known cause. Sperm may have reduced motility, so they are unable to physically reach the egg, or they may have collected impurities along their travel which can block them from fertilising the egg. STIs, if left untreated, can cause male infertility by scarring the vas deferens (the tubes that the sperm travel from the testicles out of the penis). Hormone imbalances can also cause infertility.^1,10

Medication 

Clomiphene is a hormone medication that can be taken to stimulate ovulation in AFAB people, and can stimulate sperm production in AMAB people. 

Letrozole is another hormone medication that can stimulate ovulation. These medications should be taken around the time of ovulation in the menstrual cycle. 

Alternatively, before treatments like in-vitro fertilisation (IVF) or egg freezing, an injection of a hormone known as HCG (Human chorionic gonadotropin) is given to stimulate hyperovulation in a controlled setting (for example, a fertility clinic). Gonadotropins can also help in male factor infertility.⁵ 

Freezing eggs or sperm

Freezing of egg cells can be done preemptively by an AFAB person, to allow future use of their own eggs should they have any problems becoming pregnant. Alternatively, those donating eggs can have them frozen for others to use should they require an egg donor. 

Sperm cells can also be frozen and kept preemptively or donated. Sperm or egg donations can be used in various scenarios such as same-sex couples attempting to conceive, or single people wanting children. DNA from the donors is screened for genetic conditions, and information about the donor such as their physical appearance is also noted. Usually, people will be able to choose which donor they would like. The embryos (using either one donor cell and one from the couple wanting the child, or using two donor cells) can then be inserted into the intended mother’s uterus.^1,2

Surgery 

Surgical procedures can assist fertility. For those with endometriosis, scar tissue that may be blocking the fallopian tubes can be removed so that eggs can travel through to the uterus. Fibroids, polyps or other physical obstructions can be removed to aid fertility, as well as alleviate pain.

For AMAB people, surgery can remove physical obstructions that may block the vas deferens or epididymis. Another procedure known as varicocelectomy can improve testicular function and the ability to create sperm. Other procedures can involve direct retrieval of sperm from the testicles if they are unable to move out themselves.^10,9

IVF (in-vitro fertilisation)

IVF is one of the most commonly known methods of dealing with infertility. 

The first step is to stimulate the ovaries with an HCG injection to stimulate ovulation. Eggs are then retrieved under anaesthesia or sedation via a needle inserted in the vagina.

The IVF process involves egg cells fertilised outside of the body, and then the fertilised eggs are allowed to grow in a laboratory until they divide to make a few cells. Once the number of cells reaches a point where it could theoretically sustain a life, it is called an embryo. 

For sperm cells that may not fertilise with an egg on their own, there is a technique known as intracytoplasmic sperm injection (ICS), where the sperm cell is directly injected into an egg cell. This is used in cases of male factor infertility where sperm may be immotile.¹²

Usually, multiple embryos will be screened for certain genetic diseases and then viable embryos will be inserted into the uterus of the AFAB person intending to carry the embryo. In order for the person to become pregnant, the embryos will need to implant themselves into the uterus. Implantation is a critical stage of IVF where people may encounter failure.

The success of IVF relies on both the mother having a good-quality endometrium to allow for implantation, and the embryo being of good quality itself. Recurrent IVF failure is usually defined as 3-4 cycles of IVF that have not resulted in implantation. This can be due to the mother’s uterus, the embryo, or both.^1,2 

IUI (intrauterine insemination)

IUI is also known as artificial insemination. It is a less invasive and more cost effective alternative to IVF. IUI involves sperm placed inside the uterus of an AFAB person via a catheter (a small tube). It usually does not require anaesthesia and causes mild discomfort. The sperm are treated to separate the healthy sperm from debris and from immotile sperm. 

IUI is particularly effective in those who have normal fallopian tubes to allow the egg to reach the uterus (but have some other issues like cervical scarring). It also works well for mild male factor infertility where there is still enough good-quality sperm. 

IUI may be carried out without HCG injections, but they can be used if conception is unsuccessful. Success rates and evidence are conflicted on IUI, but it is generally regarded as a more appropriate first-line method of treatment compared to IVF. 

However, for those with scarring of the fallopian tubes, or with severe male factor infertility, or for AFAB people over the age of 35, IUI may not be an option (due to the reduction in egg quality).^3,7

Surrogacy

Surrogacy involves the embryos (either from the couple themselves or from a donor) being inserted into the uterus of a different AFAB person (the surrogate mother) who will then become pregnant with the foetus (providing implantation is successful). This foetus is not genetically related to the surrogate mother. 

Along with implantation, a critical determinant of success is the agreement (or not) of the surrogate mother. Laws are different from country to country, but in countries such as the UK or Canada, the surrogate mother is actually the legal parent of the baby and not the biological parent.

The surrogate mother has the right to keep the baby for themselves or change their mind about the surrogacy at any time (such as terminating the pregnancy). In the US, certain states do have legally binding surrogacy agreements, so that the mother has to hand over the child, and therefore success rates of surrogacy are much higher over there than in countries without such surrogacy agreements, such as Canada.¹¹

Summary 

Infertility may be due to many reasons, but the main causes in those assigned females at birth are endometriosis or PCOS. In those assigned males at birth, low sperm count or motility, and untreated STIs can cause infertility. 

Treatments most commonly are in-vitro fertilisation (growing embryos from a sperm and egg outside the body, then inserting said embryos back into the uterus), intrauterine insemination (inserting sperm into the uterus via a tube), surgical procedures to remove physical obstructions, using donor eggs/sperm, or a surrogate mother.