Team:Bielefeld-CeBiTec/Background

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Background

How it all started: Struggling with side effects caused by the pill

It all started during a talk between us team members. Some of our team members have previously experienced side effects by taking the pill. However, when looking for alternatives to the pill you will quickly find that these are not ideal either. For example alternatives like IUD (intrauterine device), based on a copper coil - which is inserted in the uterus - are not suitable for everyone. Additionally, we talked about sensiplan®, a method where the female cycle is tracked by monitoring secondary parameter like temperature and cervical mucus. But this method also has several disadvantages including that the parameter: the observation should occur at the same time and the parameter could get falsified for instance by illness, alcohol consumption, disturbed night's sleep, stress, changed environment and others [1]. We realized that contraception is a difficult topic with major potential for potential.

Why think about a new contraception method? Because a better one is needed!

There is no optimal contraception method that works for everybody. Our goal was to develop a solution that promotes gender equality by not intervening in health and supports self-determination of the user.


Don`t take your hormones, measure them!

But first: The current options of contraception

Contraception is a demanding topic. Today´s contraceptive strategies often include invasive methods or the suppression of the natural menstrual cycle. In Europe, the most commonly used contraceptive for women is the hormonal pill.

Figure 1 Worldwide frequency of contraceptive methods [2].

The insertion of an IUD (intrauterine device) or other invasive methods are also common [2]. Taking the pill can cause severe side effects including, migraine (1 of 100), weight change (1 of 100), depressive mood (1 of 100), mycosis (1 of 100) or even thrombosis (1 of 1000) and strokes (1 of 1000) [3]. The most common hormone-free alternative, the insertion of a copper IUD is also not side effect free. It can cause side effects such as increased bleeding and increased menstruation pain [4].

The menstrual cycle

Figure 2 Simplified illustration of the menstrual cycle.


The duration of the menstrual cycle is between 25 to 30 days and can be divided into three phases: follicle phase (1), ovulation (2) and luteal phase (3) (Fig. 1). A new cycle begins with the menstruation within the follicle phase. In this phase the follicle matures, the estrogen concentration rises, resulting in increasing luteinizing hormone (LH) release. During this time, the body begins to build up the endometrium. This leads to the second phase, the ovulation in which a pregnancy is possible.

However, it is important to remember that intercourse before ovulation can result in a pregnancy, as sperm can survive in the cervical mucus for several days prior to ovulation [1]. The ovulation leads to the luteal, the last phase.

Here two scenarios are possible: (1) The degradation of the follicle or (2) the implantation of the fertilized ovary into the endometrium. In this case, the follicle turns into corpus luteum which produces progesterone. If fertilization does not occur, the endometrium is rejected, menstrual bleeding begins, marking the start of the new cycle. Hormonal concentration curves can be used for contraception because the peaks indicate the point of time of ovulation of ovulate i.e. fertile time in the cycle [4,5].

Figure 3 Female reproductive organs and the course of the menstrual cycle.


The measurement of the three hormones oestradiol, progesterone and LH in the urine can be used to determine the three menstrual phases and thereby the fertile phase can be determined. The progression of their concentrations can be found below.

Figure 4 Hormone concentrations (LH, estradiol, progesterone) of the three phases of the menstrual cycle: follicular phase, ovulation, luteal phase. Based on source [5]. The blue indicates fertile phase.


Our Project

The measurement of the three hormones oestradiol, progesterone and LH in the urine can be used to determine the three menstrual phases and thereby enable the determination of the fertile phase.

We use hormone specific nanobodies and single-chain variable fragments (scFv) for the detection of the hormone concentrations in the morning urine. Combined with the surface acoustic wave (SAW) technology, this delivers a sensitive and specific device for determining the fertility. By linking SAW and the antibodies with an app, we create a user-friendly application and easy display of the fertility status.

References

[1] Arbeitsgruppe NFP, Natürlich und sicher - Das Praxisbuch, 20th ed. TRIAS, 2018.
[2] Contraceptive Use by Method 2019. 2019.
[3] STADAPHARM GmbH, “GEBRAUCHSINFORMATION: Information für Anwenderinnen Stella STADA,” 2018. [Online]. Available: https://www.stada.de/media/produkte/dokumente/gebrauchsinformationen/STELLA_0-03_2MG_FTA_SD_DE_WebPIL_9280542_1905.pdf. [Accessed: 17-Oct-2020].
[4] D. Hubacher, P. L. Chen, and S. Park, “Side effects from the copper IUD: do they decrease over time?,” Contraception, 2009.
[5] J. Roos et al., “Monitoring the menstrual cycle: Comparison of urinary and serum reproductive hormones referenced to true ovulation,” Eur. J. Contracept. Reprod. Heal. Care, 2015.