Facts on Ovulation and Infertility

What does fertility actually mean?

Fertility is your natural ability to establish a pregnancy. It can often be something we take for granted and it may only be when planning for a pregnancy that underlying issues become apparent. In this post, we will take you through the different types of infertility and potential signs of fertility problems that you can look out for.

What is infertility?

Infertility is defined as the inability to become pregnant despite regular and unprotected sex for at least a year (1). This means sex without birth control, two to three times a week, beginning shortly after your period.

How many types of infertility are there?

Infertility can be primary or secondary. Primary infertility is defined as failing to become pregnant when never having previously conceived (1). Secondary fertility means that you have previously achieved a pregnancy but are now unable to. Both of these terms can be used to classify different types of infertility in females and males. Subfertility is another commonly used term which can be used interchangeably with infertility (1). Sterility describes permanent infertility.

What are the main causes of fertility issues?

Before we explore common causes of infertility, it is helpful to remind ourselves of the main steps that are involved in creating a pregnancy. -

• Ovulation (release of the egg cell) and transport of the egg through the Fallopian tube towards the uterus

• Production of sperm and entry and transport through the female reproductive tract

• Fertilisation -  fusion of the egg and sperm in the Fallopian tube

• Implantation - attachment of the fertilised egg to the wall of the uterus

Unsurprisingly, problems with any step in the process can lead to infertility. Infertility can be a result of many different factors and can also be a combination of issues arising from both partners.

Most causes of female infertility are caused by problems with ovulation (2). Anovulation is a menstrual cycle with no ovulation, also known as an anovulatory cycle. Without ovulation there is no egg released for fertilisation and pregnancy cannot occur. Anovulation happens when there is an imbalance of hormones. The most common cause is the hormonal disorder polycystic ovarian syndrome (PCOS) (2). In the ovary, the eggs develop inside structures known as follicles. It is thought that the imbalance of hormones (in particular androgens - such as testosterone) prevent the ovarian follicles from developing properly, which can often lead to infrequent ovulation or anovulatory cycles (3).

Anovulation can also be caused by a number of different lifestyle factors - all of which can impact your hormone cycles - you can read more about this in our article Diversity in Menstrual Cycles. These include prolonged periods of stress, disrupted sleeping, reduced calorie intake, and excessive exercise. Excessive exercise can lead to increased levels of the stress hormone cortisol (4). Cortisol reduces the amount of a hormone known as gonadotropin releasing hormone (GnRH) which in turn impacts the level of two hormones (FSH and LH) both of which are important for the growth of follicles and the release of an egg at ovulation.

It is important to note that certain types of hormonal birth control also work by suppressing the hormonal changes that regulate ovulation. For example methods that use a combination of estrogen and progesterone such as the combined oral contraceptive pill prevent ovulation (5). Other methods which only contain progesterone, such as the mini pill and the hormonal intrauterine device, can prevent ovulation in some people but usually work via other mechanisms.

A woman’s age also affects her fertility. In fact it is the most important factor in determining a couple’s fertility (6). Women are born with a limited supply of eggs and this pool decreases with age - resulting in fewer, lower quality eggs available for ovulation (7). This results in a higher chance of anovulatory cycles, which increases as you approach menopause. Other less common causes of infertility in women include:

• Endometriosis - a condition in which endometrial-like tissue grows outside the uterus (can lead to infertility in multiple ways including interfering with follicle development and preventing implantation of the fertilised egg)

• Blocked Fallopian tubes due to endometriosis or pelvic inflammatory disease (the most common cause is infection with Chlamydia trachomatis). Infections and their side effects are a common cause of secondary female fertility (8)

• Structural abnormalities of the uterus, uterine fibroids or reduced receptivity of the uterus to the fertilised egg

Male infertility is believed to account for 20-30% of cases of infertility (9). Common causes include low sperm count, abnormal sperm appearance, blocked sperm ducts or poor sperm motility. Problems with any of these aspects will reduce the likelihood of fertilisation.

What types of fertility tests are there?

Initial fertility tests usually focus on the male partner as these are often considered the least invasive. They involve analysing a semen sample by examining the number of sperm as well as looking for abnormalities in their appearance (known as morphology) or irregularities in their motility.

Tracking ovulation

When assessing fertility in the female, the first step will typically investigate whether ovulation is taking place (2). This can be done using fertility-awareness methods which can involve daily tracking of basal-body temperature often in combination with changes in cervical mucus. Home ovulation tests can additionally be to measure the mid-cycle peak of luteinising hormone (LH) which occurs just prior to ovulation.

Ovulation can also be detected by measuring progesterone levels. Progesterone is the hormone released by the corpus luteum which is the structure left over after ovulation (10). During the second half of the cycle progesterone levels increase, offering a measurable way of confirming that ovulation has taken place. Progesterone levels are conventionally measured in the clinic using a blood sample taken during the mid-luteal phase of your cycle. However, saliva measurements can be an alternative and non-invasive way of tracking hormone changes across the cycle which we will discuss later.

Ultrasounds can also be used as a way to assess whether normal follicle development and ovulation is taking place, by monitoring the growth and disappearance (which would indicate ovulation has taken place) of the growing ovarian follicle. Pelvic ultrasounds also offer a way to examine the uterus and Fallopian tubes.

Other types of fertility tests

If ovarian function appears normal, there are a number of other tests that can be carried out including (2):

• Hysterosalpingogram - a type of x-ray used in combination with the injection of a contrast dye into the uterus to detect any abnormalities in the uterine cavity. When the fluid passes out of the uterus and through the Fallopian tubes it can also be used to ensure there are no blockages

• Laparoscopy - inserting a thin tube with a camera through a small incision to examine your uterus, Fallopian tubes and ovaries. It can be used to identify endometriosis and scarring caused by infections

What are signs of fertility problems?

The obvious sign of issues with fertility is not becoming pregnant after a period of regular unprotected sex. However there are other signs you can look out for before this, including:

• Infrequent or irregular menstrual cycles (those that are very short or very long) can mean that ovulation is occurring infrequently or not at all

• Heavy or painful periods can be an indicator of endometriosis

• Hormone fluctuations which you may experience as unexplained weight gain, acne or facial hair

How can inne help?

Ovulation problems, including anovulatory cycles, are the most common reason for infertility. Unless you are tracking your ovulation however, you may be unaware that you are experiencing issues. This is because there is often still bleeding in anovulatory cycles. Normal menstrual bleeding is a result of a drop in progesterone that occurs because of the breakdown of the corpus luteum. As there is no progesterone in an anovulatory cycle, the bleeding - known as estrogen breakthrough bleeding - is caused by the inability of estrogen to support the growing endometrium (11).

Period tracking can help you keep a record of the frequency and length of your cycle but may not be enough for you to identify an anovulatory cycle. While inne can’t be used as a fertility test, the minilab can be used as a way to confirm that ovulation is taking place. inne makes use of a non-invasive saliva sample to measure changes in your daily levels of progesterone. By building a baseline during the first half of your cycle, the system can then detect the increase in progesterone levels that take place during the second half, after ovulation has taken place. Through regular use, inne creates a personal record of your cycle making it easy for you to recognise or identify any irregularities.

What are the treatment options for infertility?

Depending on the underlying problem, there are a number of effective treatment options that can increase your chances of getting pregnant.

Medication

Certain medications such as clomiphene can be used to induce ovulation (12). Clomiphene blocks the body’s response to estrogen. This suppresses further production of estrogen causing the pituitary gland to produce more follicle stimulating hormone (FSH), which promotes the growth of the follicles containing eggs within the ovary.

Surgery

Laparoscopic surgery can be used to correct structural abnormalities of the uterus. Surgery can also be used to remove fibroids or scar tissue that has formed as a result of previous pelvic infections or endometriosis.

Assisted conception

Intrauterine insemination, also known as IUI, is a process in which a sperm sample is washed and concentrated and placed directly into the uterus around the time of ovulation. UIU can also be used in combination with medication that stimulates ovulation such as clomiphene (2).

Assisted reproductive technology (ART) includes a number of different methods that involve handling of the egg and sperm outside your body. ART may be necessary if you are suffering from blockages in both Fallopian tubes or if your partner has a poor semen quality including low sperm count.

In vitro fertilisation, commonly known as IVF, is a form of ART. It involves retrieving mature eggs from the woman, fertilising them outside the body in the laboratory with sperm, then transferring the embryos into the uterus. If sperm motility is impaired IVF can be combined with intractyoplamic sperm injection (ICSI) which involves direct injection of the sperm into the egg (2). Depending on the underlying cause of the infertility, ART procedures can also be carried out using donor eggs or sperm or embryos.

Experiencing problems with your fertility can feel overwhelming but you must remember that you are not alone. Infertility is a common problem and is estimated to affect up to 9% of couples worldwide (6, 8). If you feel you are experiencing problems it is important that you talk to your healthcare provider early to discuss your possible treatment options.

References

1. Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, Rienzi L, Sunde A, Schmidt L, Cooke ID, Simpson JL, van der Poel S. The International Glossary on Infertility and Fertility Care (2017). Hum Reprod. 32, 1786-1801.

2. Walker MH & Tobler KJ. Female Infertility. In StatPearls (Updated 2020).

3. Franks S and Hardy K (2018). Androgen Action in the Ovary. Front. Endocrinol. 9:452.

4. Gibson MES, Fleming N, Zuijdwijk C & Dumont T (2020). Where Have the Periods Gone? The Evaluation and Management of Functional Hypothalamic Amenorrhea. J Clin Res Pediatr Endocrinol. 12, 2020, 18-27.

5. Rivera R, Yacobson I, Grimes D. The mechanism of action of hormonal contraceptives and intrauterine contraceptive devices (1999). Am J Obstet Gynecol. 181, 1263-1269.

6. Balen, AH & Rutherford, AJ (2007). Management of infertility. BMJ. 335, 608–611.

7. Broekmans FJ, Knauff EA, te Velde ER, Macklon NS, Fauser BC. Female reproductive ageing: current knowledge and future trends (2007). Trends Endocrinol Metab. 18, 58-65.

8. Vander Borght M, Wyns C. Fertility and infertility: Definition and epidemiology (2018). Clin Biochem. 62, 2-10.

9. Leslie SW, Siref LE, Khan MAB. Male Infertility. In StatPearls (Updated 2020).

10. Reed, B. G. & Carr, B. R. The normal menstrual cycle and the control of ovulation. In Endotext (eds. De Groot, L. J., Chrousos, G. & Dungan, K., 2015)

11. Jones K, Sung S. Anovulatory Bleeding. In: StatPearls (Updated 2020).

12. Legro RS. Ovulation induction in polycystic ovary syndrome: Current options (2016). Best Pract Res Clin Obstet Gynaecol. 37, 152-159.