Tests during the medical use of Menotropin (hMG)

Treatment with menotropin (hMG) is impossible without tests: they are precisely what determine the starting dose, the timing of the trigger and the safety of the whole cycle. Whereas for many drugs laboratory monitoring is an optional extra, for gonadotropins it is part of the treatment itself. The editorial team explains which tests are done at each stage, in women and men, and what their results mean.

Why hMG cannot be "managed blindly"

The ovarian response to menotropin varies several-fold between women. One patient responds to the same dose with three follicles, another with twenty. Both the effectiveness and the risk of ovarian hyperstimulation syndrome depend on this. That is why treatment begins with a prediction of the response, and then, daily or every other day, the prediction is checked against reality.

For men the situation is different: the effect of menotropin appears slowly, and monitoring is needed not daily but at intervals of months. But here, too, it is impossible without tests to understand whether the treatment is working and whether it is worth continuing.

The ESHRE guideline (2020) pays particular attention to which tests have evidence-based value for planning stimulation and which add no useful information. This approach helps avoid unnecessary tests and focus on those that actually change decisions.

Below we will consider the tests in logical order: before treatment, during stimulation, in the event of complications, and after completion.

Assessment of ovarian reserve

The first step is to understand how many follicles are capable of responding to stimulation. Two main markers are used for this: anti-Mullerian hormone (AMH) in the blood and the antral follicle count (AFC) during transvaginal ultrasound at the start of the cycle. ESHRE considers precisely these to be the most informative for predicting the response.

High AMH and a large number of antral follicles, characteristic of polycystic ovary syndrome, indicate a risk of an excessive response. In such patients, lower starting doses and protocols that allow the hCG trigger to be replaced are chosen. Low values, on the contrary, predict a weak response.

It is important that reserve markers predict the number of eggs but not their quality or the chances of pregnancy as such. A woman with low AMH can become pregnant, and a high number of follicles does not guarantee success.

Besides hormones, a general examination is carried out before treatment begins: blood type, infection screening and, when indicated, assessment of the fallopian tubes and the uterine cavity.

Monitoring during stimulation

During stimulation the main tool is serial ultrasound examinations. The doctor measures the number and diameter of follicles and the thickness of the endometrium. The first monitoring ultrasound is usually done a few days after the start of the injections, then at an interval that depends on the rate of growth.

Estradiol in the blood reflects the combined activity of the follicles. A very rapid rise or excessively high values is a signal of the risk of OHSS. The ratio of estradiol to the number of mature follicles also helps to assess whether the follicles are functionally sound.

Progesterone is measured on the day of the trigger in many clinics: its premature rise can impair the receptivity of the endometrium. In that case it is sometimes recommended to freeze the embryos and transfer them in the following cycle. LH is monitored so as not to miss a premature peak, especially in protocols without GnRH analogues.

On the basis of this data, the doctor adjusts the dose of menotropin, decides when to administer the trigger and whether it is safe to continue the cycle at all. In the event of an excessive response, the cycle may be canceled — this is unpleasant, but it protects against severe complications.

Tests when OHSS is suspected and after the cycle

If bloating, pain, nausea or shortness of breath appear after the trigger, the scope of examination is expanded. The ASRM guidelines (2016) define the laboratory signs of the syndrome's severity.

• Complete blood count:elevated hematocrit and leukocytosis indicate hemoconcentration.
• Biochemistry:sodium, potassium, creatinine, urea, liver tests, albumin.
• Coagulation panel:when indicated, to assess thrombotic risk.
• Ultrasound:the size of the ovaries, the presence and volume of ascites, pleural effusion.
• Urine output and body weight:daily, at home or in hospital.

Pregnancy is diagnosed by beta-hCG in the blood at a time determined by the clinic. If the trigger was hCG, early tests can be false-positive, so it is not a single result but the trend that matters.

If the test is positive, further monitoring includes repeat hCG tests and an early ultrasound to confirm intrauterine location and the number of gestational sacs.

After an unsuccessful cycle, the tests help to assess the response and adjust the next protocol: the number of oocytes retrieved, the estradiol trend, the presence of complications.

Tests in men

In men with hypogonadotropic hypogonadism, menotropin is used together with hCG to initiate spermatogenesis. Before treatment, testosterone, LH, FSH, prolactin and other pituitary hormones are assessed, an MRI of the pituitary is done when indicated, the volume of the testes is measured, and a semen analysis is performed. The Endocrine Society guideline (Bhasin et al., 2018) recommends gonadotropins for men with this diagnosis who wish to father children.

During treatment, testosterone (to ensure that the hCG component provides sufficient stimulation), estradiol and hematocrit are monitored. Spermatogenesis is a slow process: the development cycle of a spermatozoon lasts about two and a half months, so the first informative semen analyses are usually done only after a few months.

In the study by Liu and colleagues (2009), the prognosis for achieving spermatogenesis depended on the baseline volume of the testes and on whether puberty had been spontaneous. The doctor takes these factors into account when explaining the expected timeframe to the patient.

When spermatozoa appear in the ejaculate, some clinics offer to cryopreserve them as insurance. Regular semen analyses help to decide whether natural conception is possible or whether assisted reproductive technologies are needed.

Editorial conclusions

Laboratory and ultrasound monitoring is an integral part of treatment with menotropin. Before stimulation, AMH and the antral follicle count are key; during it, serial ultrasound scans, estradiol and, in many clinics, progesterone on the day of the trigger.

When OHSS is suspected, the examination is expanded to include hematocrit, electrolytes, creatinine and liver tests. In men, the main measures are testosterone, hematocrit and a semen analysis at intervals of a few months.

The interpretation of these tests is possible only in combination with the clinical picture and the protocol, so it is carried out by a doctor.

We also recommend reading our articles on the tests used with hCG, on menotropin in women, and on the effect of menotropin on the liver and kidneys.

References

1. Bosch E, Broer S, Griesinger G, et al. ESHRE guideline: ovarian stimulation for IVF/ICSI. Hum Reprod Open. 2020;2020(2):hoaa009.
2. Practice Committee of the American Society for Reproductive Medicine. Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome: a guideline. Fertil Steril. 2016;106(7):1634–1647.
3. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715–1744.
4. Liu PY, Baker HW, Jayadev V, et al. Induction of spermatogenesis and fertility during gonadotropin treatment of gonadotropin-deficient infertile men: predictors of fertility outcome. J Clin Endocrinol Metab. 2009;94(3):801–808.
5. Інструкція для медичного застосування (SmPC) препаратів менотропіну (високоочищений ХМГ, напр. Menopur). Ferring Pharmaceuticals.
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