“If I reduce my weight with Mounjaro or Wegovy, will I get pregnant better?” This is the question most frequently thrown recently by women experiencing obesity and infertility together. As GLP-1 class obesity treatments show rapid weight loss effects, expectations are also growing that they will increase the possibility of pregnancy. However, for women preparing for pregnancy, weight loss and obesity treatments are an area that cannot be approached simply as a ‘matter of losing weight’. This is because the timing of treatment, the point of drug discontinuation, and even the effects on ovulation and pregnancy must be meticulously weighed.
Just how much does obesity affect a woman’s reproductive ability? Can weight loss be the answer to infertility treatment? Gaining weight is not a matter of just body weight increasing. For women, it is a problem that can even shake the balance of the body preparing for pregnancy. In the past, obesity was regarded merely as a risk factor for chronic diseases like diabetes or high blood pressure, but recently, a perspective viewing it as one of the important causes causing ovulation disorders and infertility is growing.
In that sense, regarding the obesity treatments spreading like a trend recently, infertility doctors are putting in a sharp reminder that a cautious approach is necessary, even if they say it helps. If so, what efforts should obese infertile women make for pregnancy? We met Director Park Chan-woo of Seoul I& Women’s Clinic and heard the answer to that.
▼ It is said that more than one out of three adults is classified as obese. If body fat is excessively accumulated, what kind of effect does it have on reproductive function? “Obesity is not simply a problem of weighing a lot. Fat is a single endocrine organ that secretes hormones in our body. When body fat increases excessively, the balance of reproductive hormones begins to collapse. For women, ovulation becomes irregular and the possibility of the egg’s quality degrading grows. Cases where Polycystic Ovary Syndrome (PCOS) worsens or ovulation stops are also not few. The implantation environment of the endometrium also receives the effect, making it difficult for the fertilized egg to catch a spot. The same goes for men. As abdominal obesity becomes severe, the male hormone testosterone decreases, and the phenomenon of male hormones converting to female hormones in fat tissue increases. Imagine female hormones becoming abundant in a man. Isn’t that a big deal? Sperm count and motility drop, and the DNA damage rate of sperm can also become high.”
▼ I heard there are many cases of being obese while having Polycystic Ovary Syndrome (hereafter PCOS). “Actually, one of the combinations most commonly met in the infertility outpatient clinic is obesity and PCOS. Of course, there are many thin body types with PCOS, but as weight increases, there are many cases where symptoms become more severe. In particular, abdominal obesity increases insulin resistance. When insulin is excessively secreted, the production of male hormones (androgens) in the ovaries increases. When male hormones become abundant, follicles fail to mature normally, causing ovulation disorders, and the ovaries become full of small follicles that failed to ovulate.”
▼ In a word, are you saying obesity is an important risk factor and an aggravating factor for PCOS? “There are thin PCOS cases too, but there are more cases where one gains more weight because of PCOS. In PCOS, insulin resistance is common, so weight easily increases. Due to the increase in male hormones, abdominal obesity easily becomes severe. Ultimately, obesity worsens PCOS, and PCOS in turn makes obesity severe.”
▼ This thing called insulin resistance does not exactly hit home. By what mechanism are insulin and obesity connected? “To speak easily, insulin is like a doorbell knocking on the door of a cell. It plays the role of sending a signal saying, ‘Please open the door’ so that glucose in the blood can go inside the cell and be used as energy. However, when insulin resistance occurs, the cell does not react well even when the doorbell is pressed. Since the door does not open by pressing it once, the body keeps pressing the doorbell, and as a result, insulin is excessively secreted. The problem is that the overflowing insulin does not just regulate blood sugar but also gives an effect to the ovaries. As insulin concentration becomes higher, the ovaries make more male hormones, and the follicles cannot grow normally. Ultimately, ovulation does not occur well, which can lead to irregular menstruation or PCOS. Insulin resistance becomes one of the root causes interfering with pregnancy.”
▼ Aren’t there cases where one is obese but not PCOS? In the case of an obese woman who is not PCOS, why can she become infertile? “Sufficiently so. Not all obese women possess PCOS. Even so, cases where pregnancy does not occur well are not few. This is because obesity exerts various effects on the reproductive function itself, regardless of PCOS. The biggest problem is chronic inflammation and hormone imbalance. When fat tissue becomes abundant, substances causing inflammation are continuously secreted, and the balance of female hormones also begins to shake. As a result, the quality of the egg can drop and ovulation function can decline. Even if fertilization occurs, the implantation environment of the endometrium worsens, so the possibility of leading to pregnancy can become low. Similar results come out in test-tube baby procedures (IVF) as well. Obese women often use more ovulation-inducing agents, and there are cases where egg retrieval is not easy. Even if an embryo is made, the implantation rate and birth rate are somewhat low, and after pregnancy, the risk of complications like miscarriage, gestational diabetes, and pregnancy toxemia (preeclampsia) also becomes high. Ultimately, the effect of obesity is not a problem of just ovulation. It is important to understand that it can give an effect to the entire process of pregnancy, from the egg’s quality, endometrium, implantation, until pregnancy maintenance.”
▼ It is said that male obesity is also a cause of becoming infertile. “That is so. Infertility is not solely a woman’s problem. Actually, in close to half of couple infertility, the male factor is involved independently or complexly. However, many men still do not know well the fact that obesity gives an effect to reproductive ability. For men, as abdominal obesity becomes severe, testosterone decreases, and the phenomenon of male hormones converting to female hormones in fat tissue increases. When the hormone balance collapses like this, the function making sperm can drop. Another important thing is the temperature of the testicles. Sperm is made best in an environment 2~3 degrees lower than body temperature. When thigh and abdominal fat increase due to obesity, the temperature around the testicles goes up, becoming a disadvantageous environment for sperm creation. If chronic inflammation and oxidative stress are added here, not only sperm count and motility but also the DNA damage rate can become high. Actually, when trying a semen test, we often see cases where sperm concentration or motility is dropped in obese men. Of course, not all obese men are infertile, but if pregnancy is not occurring well, men too must think of weight management and lifestyle habit improvement as one important axis of treatment.”
▼ In the case of obesity, if you only say “Lose weight” as an infertility doctor, wouldn’t it be too irresponsible? “I think so too. If you are an infertility doctor, you shouldn’t finish the medical treatment by saying ‘Go lose weight first and come back’ to the patient. So, I do the approach of ‘Let’s make a body capable of pregnancy together’. We check lifestyle habits one by one, prescribe exercise, correct dietary habits, and when necessary, even agonize over obesity treatment together. The patient and I must become one to be able to improve it. We must also be cautious about unconditionally repeating only test-tube baby procedures (IVF). If infertility is approached only as a technical problem of eggs, sperm, and implantation, the patient experiences greater frustration when the treatment fails. This is because repeating only the procedure while the body is exactly the same does not mean the result will become different. I think infertility treatment is not a technique making an embryo, but a process of making a body capable of pregnancy. When metabolic health becomes good, hormone balance is recovered, and inflammation is reduced, the success rate of test-tube baby procedures as well as natural pregnancy can heighten together. That is why I am doing the treating of the body and mind first.”
▼ Recently, the Mounjaro and Wegovy fever among obese men and women is incredible. While preparing for IVF, is it okay to receive a prescription for weight reduction? “Because the weight reduction effect of ‘Wegovy’ and ‘Mounjaro’ injections is so dramatic, these days the cases of overweight people wanting to receive a Wegovy or Mounjaro prescription, saying they will lose weight and do IVF, have suddenly increased. It seems even more so because cases of the so-called ‘GLP-1 baby’—where natural pregnancy occurred while being hit with Wegovy or Mounjaro—are surging rapidly, especially centered around overseas SNS. It is because irregular menstruation gets resolved as weight is lost and insulin resistance is improved. In particular, women who are Polycystic Ovary Syndrome (PCOS) have their ovulation function normalized, so the possibility of pregnancy goes up. Actually, obesity is a major cause of infertility inducing degradation of egg quality or ovulation disorders. Even doing just a little weight reduction definitely becomes a big help to pregnancy. However, in the case of getting hit with Wegovy or Mounjaro injections, there is a fatal precaution you must absolutely know and pass by. Because it makes the stomach’s movement slow, the absorption rate of contraceptive pills eaten through the mouth drops, so the probability of failing at contraception becomes high. Above all is the fact that the safety of Wegovy or Mounjaro drugs exerted on the fetus has not been perfectly verified yet. Therefore, even if you get hit with the injection, you must attempt pregnancy after it has completely slipped out of the body.”
▼ In the case of getting hit with Wegovy or Mounjaro injections, how should IVF be adjusted? “Wegovy (ingredient name: Semaglutide) must be stopped at least 2 months (8 weeks) prior to pregnancy attempt. The period the drug ingredient stays inside the body is on the long side. Since it takes over 5 weeks just to completely disappear, you must stop the medication administration safely at least 2 months prior. Mounjaro (ingredient name: Tirzepatide) must be stopped at least 1~2 months prior to pregnancy attempt. According to the standard of health authorities of each country, stopping the medication administration at least 4 weeks, and safely 8 weeks prior, is recommended.”
▼ In IVF (test-tube baby procedure), frozen embryo transfer is done a lot recently. Even if you only do egg retrieval and delay the embryo transfer, do you still have to do it a long time after cutting off the Wegovy or Mounjaro injection? “That is so. It is because of anesthesia. Wegovy and Mounjaro make the speed at which the stomach empties very slow. So, if you do sleep anesthesia for egg retrieval in this state, a dangerous situation called ‘aspiration pneumonia’ can occur, where food that remained in the stomach flows backwards and enters the lungs. This is exactly the reason why the American Society of Anesthesiologists (ASA) is recommending that you must absolutely stop drug intake at least 1 week before doing a procedure accompanied by anesthesia. More conservative and thorough fasting preparation than the general fasting time (8 hours) is necessary. Also, you must absolutely inform the attending physician and the anesthesiologist of the drug intake fact in advance.”
▼ It seems the core is that large-scale research on what kind of effect obesity treatments exert on the effect of controlled ovarian hyperstimulation injections or ovarian response is still lacking. “That is so. Infertility doctors are recommending to temporarily stop obesity treatments from the point of starting controlled ovarian hyperstimulation injections (like the start date of menstruation). If appetite drops due to the drug effect and meal volume is extremely limited, essential nutrients for welcoming a baby, such as protein, folic acid, iron, and vitamins, become insufficient. If it becomes like this, it can rather drop the quality of the egg (Egg Quality), so balanced nutritional intake must be accompanied.”
▼ No matter how quickly overweight or highly obese women want to do pregnancy, they must be careful about drug input for weight reduction. “Let’s recall the ultimate goal of obesity treatment. Isn’t it pregnancy success (childbirth)? Therefore, do not be too attached to simply reducing the number on the scale, but making a safe and warm body so you can meet a healthy pregnancy and a healthy baby is the core. Before receiving a drug prescription, an infertility specialist and an obesity treatment specialist must absolutely put their heads together and design a treatment roadmap reaching from medication administration, drug holiday and contraception, to infertility procedure.”
▼ Is doing weight reduction with exercise and dietary regulation the only best for pregnancy? “Exercise and dietary regulation are the most basic and yet the most important treatment. However, reducing the number on the scale is not the goal. Recovering a healthy metabolic state and making a body capable of pregnancy is the goal. Actually, patients whose ovulation starts again and menstrual cycle gets normalized just by reducing 5~10% of their current weight are not few. Even in test-tube baby procedures, we frequently experience cases where the possibility of pregnancy heightens by reducing weight first, rather than making one more embryo. However, the same method cannot be applied to all patients. Time is different for those in their 20s and 40s, and the strategy for a patient with good ovarian function and a patient with degraded ovarian function must also be different. For a certain patient, it is helpful to start treatment after reducing weight for a few months, but for a certain patient, it is more appropriate to proceed with weight management and infertility treatment simultaneously without delaying time. Ultimately, the important thing is not ‘how quickly you took off the flesh (weight)’ but ‘how healthily your body was recovered’. I think infertility treatment is not selecting one between weight reduction and procedure, but a process of doing both things in parallel in a balanced way fitting the patient’s situation.”
▼ Is there a standard of obesity that interferes with pregnancy? “Obesity is usually evaluated by BMI (Body Mass Index). In the Asian standard including our country, BMI 23~24.9kg/㎡ is classified as overweight, 25~29.9kg/㎡ as obesity, and 30kg/㎡ or above as high obesity. However, in infertility, we do not look at only one BMI number. This is because even for the same BMI 25, a person with a lot of muscle mass and a person with a lot of abdominal fat can have a completely different metabolic state. In particular, as waist circumference stretches and abdominal obesity becomes severe, insulin resistance and chronic inflammation increase, so it is highly likely to exert a bigger effect on reproductive function. Looking at studies, as BMI goes up to 30kg/㎡ or above, the natural pregnancy rate decreases, and even in test-tube baby procedures, the ovulation induction response and pregnancy rate drop, and the risk of miscarriage and pregnancy complications has a tendency to heighten. Therefore, in BMI 30 or above, there are many cases where weight reduction is actively recommended. However, just because BMI is normal does not mean you can be relieved. ‘Dry obesity’ (Skinny fat), where weight is normal but there is a lot of abdominal fat or metabolic abnormalities, can also give an effect to reproductive function. Ultimately, in infertility medical examination, it is important to evaluate not only BMI but also waist circumference, body composition, and metabolic health together.”
▼ While doing IVF procedures for more than 20 years as an infertility doctor, was there a most difficult case? “Degradation of ovarian function is the most difficult compared to any cause of infertility. For obesity or Polycystic Ovary Syndrome, even if it takes time, a treatment strategy can be set up while reducing weight and improving the metabolic state. Actually, cases where ovulation is recovered and it leads to pregnancy through lifestyle habit correction or drug treatment are also not few. On the other hand, degradation of ovarian function is not a disease that gets better when time passes. Because the number and quality of eggs continuously decrease as age increases, both the doctor and the patient must fight with time. No matter how good an incubator and latest technology there is, if there is no egg, IVF also has a limit. The most regrettable moment in the consultation room is when the thought ‘If only you had come a little bit earlier’ enters. The patient spent time repeating various treatments in the meantime, and there are cases where they find the hospital only after their ovarian function has hugely dropped. At that time, there are not many choices medically either. So, I say that what is more important than obesity is time. Obesity can be improved, but the time of the ovary cannot be turned back. Infertility treatment, more than waiting for the latest technology, not missing the appropriate timing is more important than anything.”