Ozempic and Fertility: Can it really help to achieve pregnancy?

What is Ozempic?

Ozempic is the trade name for a medication whose active substance is semaglutide. It belongs to the family of GLP-1 receptor agonists (GLP-1-RA), initially used for the treatment of people with obesity-associated type 2 diabetes and later for people with obesity without diabetes, commercialised for use in obesity under the name Wegovy®.

Tirzepatide is another useful drug for the treatment of obesity commercialised under the name Mounjaro® which has later appeared to increase the arsenal of useful drugs for the treatment of obesity and marketed in Spain from 1 July 2024. Unlike Ozempic/Wegovy, this is a dual agonist of GLP-1 and another intestinal peptide called GIP and trials point to greater efficacy in terms of weight loss, with a similar safety and tolerability profile.

In both cases, its prolonged action allows weekly administration.

The first GLP-1-RA commercialised exclusively for the treatment of obesity, Liraglutide (Saxenda®), remains to be mentioned. Its disadvantage compared to the previous ones is the need for weekly injections and its lower efficacy in terms of weight loss.

How does Semaglutide and Tirzepatide work?

Under normal conditions, when food is ingested, peptides are released from the gut who inform the body that the digestive tract has ‘food’ and put the body into ‘satiety mode’, including GLP-1 and GIP.

The action of these peptides can be summarised as follows

• Stimulation of insulin secretion: increases the release of insulin by the pancreas in the presence of glucose, helping to lower blood sugar levels.
• Inhibition of glucagon release: decreases the secretion of glucagon, a hormone that raises blood glucose levels.
• Delayed gastric emptying: slows stomach emptying, which may contribute to increased feelings of fullness.
• Stimulation of hypothalamic receptors in the satiety centre.
• GIP also has a direct action on adipose tissue (fat tissue).

In patients with obesity and diabetes mellitus, this regulatory mechanism may be altered.

These peptide analogues, used at pharmacological doses, achieve significant weight loss, mainly by reducing intake, as well as improving the metabolic situation in the case of diabetes or associated insulin resistance, such as in Polycystic Ovary Syndrome.

 

Where does the link between these drugs and fertility come from?

The detrimental impact of obesity on fertility in both men and women is well known.

In an attempt to improve fertility both spontaneously and after fertility treatments, we try to reduce weight in the order of 5-10% of the initial weight in people with obesity, achieving significant improvements.

Currently, with the arrival of these new treatments, we can now consider a more ambitious pre-pregnancy weight reduction, > 10%, without delaying fertility treatment for too long.

Women with polycystic ovary syndrome (PCOS) who, in addition to obesity, often have insulin resistance with impaired ovulation and difficulty in getting pregnant, may particularly benefit from this type of treatment.

We have been using Ozempic/Wegovy for years and recently Mounjaro with the aim of improving fertility through significant weight loss.

Can Ozempic or similar drugs really improve the chances of pregnancy?

Weight loss has been shown to regularise cycles and restore ovulation in some cases of women with PCOS, as well as in obese women without PCOS, favouring spontaneous pregnancies.

Furthermore, in women who have to resort to fertility treatment, the results are better after a significant weight loss, with a greater chance of achieving a newborn in the cradle, which, in the end, is what we are looking for.

In all cases, a pregnancy achieved with a better metabolic situation will also help to reduce complications during pregnancy such as gestational diabetes or pre-eclampsia, among others.

So we can say that these treatments can improve the chances of pregnancy.

Therefore, their use as part of a comprehensive treatment for weight loss and metabolic control could increase the chances of pregnancy in obese women with/without ovulation disturbances.

In the case of men, these treatments may also help to reverse hypogonadism associated with excess weight and improve sperm quality.

The Spanish Fertility Society (SEF in Spanish) emphasises the need for more studies to specifically evaluate the impact of drugs such as Ozempic on the chances of success of assisted reproduction treatments.

 

Risks of Ozempic/Wegovy and Mounjaro on fertility

Although these drugs have clear metabolic benefits, they also have risks that must be considered when treating women of childbearing age, whether or not they are intended for pregnancy.

These drugs have a long average life and their use in pregnancy is contraindicated in the absence of safety studies.

Women on these treatments may regain spontaneous fertility and become pregnant unplanned and exposed to the drug.

• Considerations

Women of childbearing age treated with this group of drugs should avoid pregnancy and should use a safe method of contraception.

• Stop treatment before pregnancy

For Semaglutide, the datasheet recommends stopping treatment about 2 months before pregnancy.

For Tirzepatide, there is no established ‘washout’ time in the datasheet.

Most fertility clinics perform the embryo transfer one month after stopping treatment. At Instituto Bernabeu we recommend 5 weeks (the first week has exposure for the last dose which lasts a week and another 4 weeks of washout).

In any case, preliminary data on unplanned pregnancies in women treated with these drugs have not shown any associated complications for the moment.

In which women is the use of Ozempic/Wegovy/Mounjaro recommended before fertility treatment as a preconception treatment?

The use of these drugs such as semaglutide and tirzepatide may be recommended in patients in whom obesity appears to be playing a role in the fertility problem.

1. Women with obesity

2. Women with PCOS and insulin resistance

3. Women with type 2 diabetes mellitus or pre-diabetes associated with obesity/overweight (the treatment sometimes manages to reverse the metabolic alteration completely after weight loss).

In all cases, weight loss prior to fertility treatment can improve oocyte/embryo quality and endometrial receptivity, reducing the risk of miscarriage, implantation failure and pregnancy complications, thus increasing the likelihood of treatment success.

What is the weight limit for starting fertility treatment?

This is a controversial topic and there is no final answer. When a woman with a desire for pregnancy has obesity and associated metabolic complications, it is clear that her fertility both spontaneously and in response to fertility treatments is compromised and she will benefit from pregestational treatment to lose weight and improve her metabolic situation.

Sometimes the possibility of fertility treatment with a Body Mass Index (BMI) > 35 kg/m2 has been discussed, but not transferring embryos until the woman has a BMI < 30 kg/m2.

At Instituto Bernabeu, we perform a complete assessment of the woman’s adiposity, which is indirectly measured by BMI and other parameters that will allow us to evaluate if the patient has any associated complications. The objective of the pre-pregnancy weight control treatment is to achieve a sufficient weight loss to minimise the risks of pregnancy and to optimise the fertility treatment (usually a weight loss of > 10% of the initial weight). In most cases it is not necessary to achieve a BMI < 30 to optimise gestation. In many cases, women stop weight loss treatment to achieve their pregnancy (the age factor is very important) and after childbirth and breastfeeding, they come back to continue their weight loss treatment until they reach more ambitious final weight goals.

Our experts’ opinion

Dr. Navarro emphasises that these medications useful in weight loss should be used under the supervision of a specialist, mostly in women seeking to improve their fertility.

We must make a complete assessment of the possible causes of obesity in order to treat them simultaneously (vitamin D deficiency, thyroid disease…).

In addition, assessment of associated complications (fatty infiltration of the liver, hypercholesterolemia or impaired glucose metabolism) must also be taken into account.

In all cases, a ‘qualitatively’ healthy diet must also be ensured. Rapid weight loss can lead to nutritional deficiencies which can take their toll during pregnancy and must be supplemented during the weight loss phase.

All of this must be complemented with physical activity to prevent muscle mass loss.

At Instituto Bernabeu we have had a comprehensive obesity management programme for many years (Endocrinology Department).

 

Recommendations before the use of GLP-1-RA drugs in women with a desire for pregnancy

• Consultation with a doctor: Before considering the use of Ozempic, Wegovy, Mounjaro or other medications, it is essential to consult with a specialist accustomed to managing Obesity in the context of fertility because of its particularities.
• Comprehensive approach: Weight loss can be beneficial, but must be part of a comprehensive plan that includes a balanced diet, regular exercise and other medical treatments as needed.
• Caution if trying to conceive: If you are planning a pregnancy, inform your doctor about any medications you are taking. In the case of these medications, it is recommended to stop taking them at least five weeks before trying to conceive.
• No self-medication: Avoid starting or stopping any treatment without the supervision of a health professional.

Dr. Pino Navarro, (Doctor Associated no. 307304), endocrinologist at Instituto Bernabeu