Clomiphene — hormonally triggering ovulation in cases of ovarian disfunction
Women who, after several months of unprotected sexual intercourse, still have not been able to achieve pregnancy often wonder what the cause is. Infertility is an elusive problem, as many different factors alone or in combination can be the cause of an unfulfilled child wish. If ovulation is absent or irregular, it can be triggered hormonally with the help of the active ingredient clomiphene.
Triggering ovulation: Hormone treatment with clomiphene
Is it the woman or the man? Is it stress? Are there disfunctions of certain hormones or is it the sperm quality of the man? The first indications of a hormone disorder can be an irregular or conspicuous cycle. A series of examinations may be necessary to get to the bottom of the problem.
Hormonal stimulation is one of the many therapies designed to address hormonal imbalance as a cause of female infertility.
In this article we discuss what clomiphene is, how and when it is used and what side effects it can have. We also look at alternatives, such as letrozole, which are used in medicine for hormone treatments among other things.
Important advance: The choice of preparation for hormone treatments always depend on the type of disorder and individual factors, which is why a prior diagnosis by a doctor is important. Doctors adapt the therapy accordingly to each patient and decide on a particular type of treatment with suitable medication.
What is clomiphene?
Clomiphene is one of the active substances prescribed to women for ovarian stimulation to trigger ovulation if they do not ovulate or ovulate irregularly. It can be used for hormonal treatments of the female cycle to trigger egg maturation on the ovaries. However, there are other drugs besides clomiphene that are prescribed for this purpose, especially for PCOS. The aromatase inhibitor letrozole is now a common alternative.
When is clomiphene used?
The active ingredient clomiphene is used in fertility treatments. Women who want to have children and who have been trying unsuccessfully for several months to become pregnant during their fertile phase should have their doctor examine them and find out about possible forms of therapy. Hormonal treatments with clomiphene may be an option to induce ovulation in women with ovarian disfunction. Ovarian disfunction is when there is no ovulation or irregular ovulation , when there are problems with the maturation of the follicles (egg sacs) or disorders of the corpus luteum phase.
There are prerequisites for clomiphene treatment  :
- Exclusion of pregnancy
- Proven functional problems of the cycle
- Tolerance of the ingredients
- Exclusion of tumours, liver diseases, ovarian cysts (exception: PCOS -> treatment only under strict medical observation)
- Avoidance of alcohol, drugs and nicotine
How does clomiphene work?
It is assumed that clomiphene inhibits the oestrogen receptors and leads to the release of gonadotropins (such as FSH and LH). The hormones released stimulate follicle maturation and lead to ovulation . Relevant steps of the cycle are shown in the following diagram. Hormonal stimulation is supposed to help with irregular or abnormal cycles. However, clomiphene does not work for every problem that affects ovulation and is most effective for PCOS as a cause. So far, letrozole has been found to be more effective for PCOS.
Clomiphene: Dosage, costs and success rate
Clomiphene should always be taken exactly as prescribed by a doctor. The dosage and duration of therapy are determined individually. Unless otherwise prescribed by the doctor, clomiphene treatment is often started on the fifth day after the start of the period. In the beginning, 1 tablet (50 mg) is usually taken once a day for 5 days. Women who have not had their period for a long time can usually start the therapy at any given time after consultation . The dosage can be higher or lower for you if your doctor prescribes a different amount for you.
The cost of clomiphene tablets can vary depending on the provider and country. As it is a prescription medicine, it can only be bought in (online) pharmacies with a valid prescription. Clomiphene is usually sold in tablet form with 25–50 mg of active ingredient. The average price is currently around 20€ — 35€ for a pack of 10 50 mg tablets (as of 22.01.2020, data subject to change).
The success rate of clomiphene treatment is usually quite high: according to studies, women with ovulation problems have up to a 70–80% chance of ovulation  . The chances of subsequently becoming pregnant are around 30–40%  .
The role of age
As you probably already know, a woman’s fertility is influenced by several factors. One of the biggest factors is age. For women over the age of 35, clomiphene can only be helpful if there is a sufficient supply of eggs to begin with. If the supply of available eggs is too low, the drug may not be successful .
Special case of PCOS: clomiphene vs. letrozole
As an alternative therapy for PCOS patients, letrozole is said to have a “more favourable side-effect profile”. Furthermore, singular follicular maturation usually occurs, which means a slightly lower rate of multiple pregnancies overall .
According to the official international PCOS recommendation guideline, the probability of multiple pregnancies in women with polycystic ovary syndrome is lower with letrozole than with clomiphene .
The rate of twin pregnancies could be compared between the clomiphene and letrozole groups in a study. The rate of twin pregnancies in pantin women on clomiphene was slightly higher (7.4%) than in those on letrozole (3.4%) .
Letrozole and clomiphene are considered first-line drugs for inducing ovulation in women with PCOS.
In Germany, the drug letrozole has so far only been approved for the treatment of breast cancer. It is therefore used “off-label” for fertility treatments .
With women affected by PCOS, the probability of triggering ovulation is higher with letrozole than with clomiphene. However, there is still no evidence that letrozole is more effective for women without PCOS.
PCOS patients with a higher pregnancy rate (per patient and per cycle) were otherwise observed with letrozole treatments compared to clomiphene . The live birth rate was also higher in the letrozole group than in the clomiphene group  .
Genadotropins can be used as “second-line therapy” if clomiphene or letrozole could not achieve the desired result .
If the attempt to induce ovulation has not been successful, the third option is assisted reproduction by IVF or ICSI, for example .
Side effects of clomiphene
During clomiphene treatment, more than 1 in 10 women may experience flushing, hot flushes and enlargement of the ovaries . Other side effects may occur in rare cases, but can be found on the relevant leaflets or from your doctor. In addition, treatment with clomiphene can lead to so-called “ovarian hyperstimulation syndrome”.
When taking clomiphene, there is an increased probability of multiple pregnancies (6–8%)  .
Problems with multiple pregnancies
The rate of multiple pregnancies is lower with treatments with the aromatase inhibitor letrozole compared to clomiphene .
The problem with multiple pregnancies during pregnancy is the risks of prematurity, increased risk of premature death and so-called “intrauterine growth restriction”, which means that the foetus does not reach its genetic growth potential.
For pregnant women, multiple pregnancies are also associated with increased cases of various, increased risks. Therefore, medical guidance and supervision is important to avoid complications.
Do you actually know how long a cycle lasts on average? When does ovulation occur, and therefore when is the best time to get pregnant? How do you determine your fertile days? In our article on the female cycle you will find the answers to your questions.
Even for women who know their cycle, it can take a little longer. Only half of all couples get pregnant during the first 3 months. After 6 months about 65% and after a year about 80% of women are pregnant . If you have been trying to get pregnant for a year without success, we recommend that you contact a specialist.
Don’t forget: Although the success rates of hormonal stimulation are high, there is unfortunately no guarantee that a pregnancy will occur.
At Fertilly, we have made it our mission to accompany couples (homosexual and heterosexual) and singles on the way to fulfilling their child wish. In doing so, it is important to us to create transparency in the area of fertility services, to provide information and knowledge on the topics of pregnancy and fertility and to help you to find the most suitable Fertility Center. Through cooperation with first-class Fertility Centres and clinics in Europe, enquiries about Fertilly are given preferential treatment. This means that our patients avoid the usually long waiting times and get appointments more quickly.
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