Low Responder & IVF treatment

Low responder

How can I become a mother if I have a bad reaction to ovarian stimulation?

It is estimated that between six percent and 36 percent of patients undergoing assisted reproduction treatment have low ovarian response. These patients, often referred to as „low responders,“ require treatment tailored to their case. In today’s article, you’ll learn all about this diagnosis and what we can do for you at Tambre if you find yourself in this situation.

What is a low ovarian response?

The definition of the term „low ovarian response“ is still controversial today. The two definitions most widely accepted by the medical community are based on the recommendations of two expert groups, namely the Bologna criteria (agreed upon by the European Society for Human Reproductive Medicine and Embryology – ESHRE) and the POSEIDON classification. (Patient-Oriented Strategies Encompassing Individualized Oocyte Number)

A patient has a low ovarian response if at least two of the following criteria are met:

  1. a) advanced age
    (b) a previous cycle of low response, that is, three or fewer oocytes obtained with a conventional stimulation protocol
    (c) decreased ovarian reserve, either an antral follicle count (AFC) < 5-7 or an AMH level< 0.5 – 1.1 ng/ml

In addition, under the Bologna criteria, it was considered that a patient with at least two low response rates to two maximal dose ovarian stimulations should also be included in this group.

As can be seen, the Bologna criteria are still very heterogeneous. To change this, the POSEIDON classification was proposed in 2016.

Four groups of patients with worsened prognosis were classified:

Ovarielle Reserve normal:

Patients Patients
up to 35 from 35
Group 1 Group 2
up to 35 years from 35 years
AFC >5 or AMH <1.2 AFC >5 or AMH >1.2
1A: <4 oocytes 2A: <4 oocytes
1B: 4 to 9 oocytes 2B: 4 to 9 oocytes

Ovarian reserve low

Group 3 Group 4
up to 35 years 35 years and older
AFC <5 or AMH <1.2 AFC <5 or AMH <1.2

What are the causes of low ovarian response?

To the surprise of many people, the aging process of the ovaries begins during fetal development. At birth, a girl has one to two million eggs. During childhood and puberty, these atrophy in large numbers before reaching a mature state.

So verfügt eine Frau bei ihrer ersten Regelblutung noch über 300 000 bis 400 000 Eizellen, von denen in jedem Zyklus 1000 ihre Follikelentwicklung beginnen und nur eine pro Zyklus zum Eisprung führt.

Parallel to this biological process, there is a loss of quality of the oocytes.

Although it is a natural process, there are diseases that lead to abrupt loss of ovarian reserve, such as endometriosis, certain ovarian surgeries, autoimmune diseases, pelvic inflammatory disease, environmental factors such as tobacco or pesticides, and other conditions that may result in lower oocyte numbers from birth, such as fragile X syndrome, 17-alpha-hydroxylase deficiency, galactosemia, or idiopathic premature ovarian failure.

What are the consequences of a low ovarian response?

Low ovarian response is not always associated with infertility. A patient with a low antral follicle count or low anti-Müllerian hormone level may not have difficulty conceiving naturally.

However, these factors may lead to a poorer prognosis in reproductive treatments such as in vitro fertilization and oocyte vitrification, as they increase the risk of cycle abortion and contribute to fewer oocytes being retrieved. This would also affect embryo numbers and pregnancy rates.

In the long term, low ovarian reserve may be associated with premature, or premature ovarian insufficiency (POI) in terms of women’s health. POI occurs when menstruation stops in patients under the age of 40. This can affect up to one percent of the female population. If the patient does not receive replacement treatment (hormone replacement therapy), POI can lead to an increased risk of cardiovascular and metabolic diseases such as osteoporosis.

What are my options if I do not respond adequately to ovarian stimulation?

Several studies have focused on this patient profile to find the best treatment approach. The experts proceed according to the following protocols:

A) Use of androgens

Androgens increase the number of follicle-stimulating hormone (FSH) receptors in granulosa cells and therefore may increase the response to FSH by acting on prenatal and antral follicles. They are mainly used in the form of topical testosterone or oral dehydroepiandrosterone (DHEA). In some recent studies, birth rates have been found to improve with the use of these medications.

B) Growth hormone (GH)

GH increases IGF-1 (insulin-like growth factor 1) in follicles, which may enhance the response to gonadotropins and also increase the ability of the oocyte to undergo cellular recovery. Subsequently, several studies have reported an improvement in the number of oocytes retrieved, the number of embryos, and in some cases, an improved clinical pregnancy rate. However, the results of the various studies are inconsistent, so the use of GH is currently experimental.

C) Double trigger

The use of human chorionic gonadotropin (hCG) is based on its biochemical similarity and binding to the luteinizing hormone (LH) receptor.
The use of gonadotropin-releasing hormone (GnRHa) agonists provides an endogenous peak of LH and FSH that is more similar to the physiological peak that occurs during natural ovulation.

Simultaneous use of both maturation strategies on the day of the trigger increases the number of mature oocytes, improves the fertilization rate, and increases the number of embryos.

D) DuoStim

DuoStim is based on the strategy of double stimulation in the same cycle. This technique (Shanghai protocol) has shown that it is possible to obtain more eggs in a shorter time, since it is not necessary to wait for the next menstruation. Compared to conventional stimulation, the results are better in terms of number of embryos and live birth rate. This is not only because a larger number of eggs are retrieved, but also because the failure rate between the first and second stimulation cycle is lower.

We hope this article has cleared up any doubts you may have about low ovarian response, and if this is the case for you, we at Tambre stand ready with open arms to give you a second opinion and Helping you finally have the baby you want so much.

Your fertility expert

The article was prepared and provided by Dr. Jana Bechthold from our partner clinic „Clinica Tambre“ in Madrid.

Thanks to our long experience as a fertility clinic in reproductive medicine, we have been able to achieve not only the highest success rates in Spain, but in all of Europe. We are pioneers in the field of artificial insemination and count on a first-class team of experts to guarantee the birth of a healthy baby.

Dr. Jana Bechthold
Dr. Jana Bechthold

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