Effect of high levels of human chorionic gonadotropin and estradiol on degree of hyperemesis gravidarum

DISCUSSION

The most frequent medical issue during pregnancy is nausea and vomiting, which is referred to as "morning sickness." Before the 20th week of pregnancy,Approximately 75% of pregnant women experience  vomiting⁹ and nausea.

Although the vast majority of pregnant women adjust to their position,  vomiting and nausea can be severe in 10% of cases, leading to nutritional issues¹⁰ .

To prevent maternal [vitamin B1 (thiamine) and K deficiency, Wernicke's encephalopathy] and fetal/neonatal [preterm birth, intrauterine growth restriction (IUGR), increased insulin resistance, psychological issues in adulthood] consequences, early detection of HG is critical¹¹.

Young age,  psychiatric disease, female fetus, nulliparity, twin pregnancy, a previous pregnancy characterized by hyperemesis and hyperthyroidism have all been recognized as risk factors for hyperemesis gravidarum¹².

The cause of HG is uncertain, though it is assumed to be caused by hormonal, metabolic, mental, and psychosomatic diseases ¹³.

Many ideas have been offered, implying its complex characterfor example, excessive levels of beta-chorionic gonadotropin (-hCG) and estradiol (E2), as well as psychological aspects¹⁴.

The study's main goal was to seehow elevated concentrations of human chorionic gonadotropin and estradiol in the first trimester increased the intensity of hyper emesis gravidarum.

This prospective study was done in El Hussein Hospital and conducted at 80 pregnant women during the first trimester of their ongoing pregnancy with HG. They were subjected to detailed history, physical examination, ultrasonography, estimate serum HCG, and Serum estradiol, a full blood count,  ketones in urine (by dipstick), creatinine, urea ands.electrolytes. An extended hospitalization was described as a stay ≥ 4 days, as this cut-off value demarcates the top quartilef or period of hospitalization in the study population.

The present study showed that the mean age, weight and GA among study cases was 26.9± 6.1 years, 67.2 ±6.8 Kg and 10.8± 5.2Weeks respectively. The median parity among cases was 2 children.

While in Atmaca et al. ¹⁰, the mean age, weight and GA among study cases was 26.54±4.64 years, 56.79±10.25 Kg and 9.18±1.93 Weeks respectively.

The results demonstrated that the mean HCG was 197434.8± 143817.9 with a median of 256127. HCG was high among 55% of cases. The mean estradiol was 2141± 946.5 with a median of 2200. Estradiol was high among 42.5% of cases. More than half of cases (51.25%) were admitted in hospital for 4 or more days which mean sever hyper emesis gravidarum.

While in Oruç et al. ¹⁵, the mean HCG was 95 415.81 ± 44719.57 and the mean estradiol was 1677.84 ± 982.5.

In this study,there was no considerable linkbetween personal and medical data on one hand (age, parity, GA, weight and Hb) and HCG level and estradiol level on the other hand, with exception of GA where it showed a positive significant correlation with estradiol level.

Our results are supported by another study in which no significantlinkage between physiological characteristics (age and weight) of respondents and HCG level ¹⁶.

From the results of this study, there was no significant correlation between HCG and estradiol level this result against the scientific background for this finding this may be because number of patients was not enough.

The results demonstrated that no significant difference between cases with hospital stay< 4 days and cases with hospital stay ≥ 4 days as regard personal and medical data (age, GA, weight and Hb and parity).

Our findings support those of Atmaca et al. ¹⁰, who found no clinically important variations in age, weight, height, gravidity, parity, or gestational age across the groups.

Unlu et al. ¹⁷ discovered that the maternal age of HG patients was substantially greater than the control group.

There was a significantly considerable impact in this study between patients with hospital stay< 4 days and cases with hospital stay ≥ 4 days as regard HCG.

The relationship between hCG release and NVP signs is largely responsible for this result,both of which reach their apex during weeks 9 and 12 of pregnancy⁸.

In a review published in 2014, 18 studies found a relationship between elevated hCG levels and NVP or HG,13 studies, on the other hand, revealed no such correlation.¹⁸.

The Generation R study examined the amount of hCG in 8,195 participants and found a connection between hCG and common NVP signs¹⁹.

Our results supported by another study where serum level of HCG was significantly associated with severity of HG ²⁰.

During a normal pregnancy, the placental tissues are densely invaded by mononuclear phagocytes and lymphocytes. trophoblast is the main origin of IL-6 during pregnancy which controls the secretion of hCG. Excessive activity of granulocytes and high concentration of trophoblast-derived cytokines might be involved in hyperemesis gravidarum. The impact of increased amounts of hCG in brain areas directly implicated in nausea or upper gastrointestinal tract or can rise thyroid hormone and estradiol which has the ability to affect nausea ²¹.

Another studydiscovered a relationship between elevated hCG levels and the incidence of HG . The peak of hCG secretion in the first trimester coincides with the time of hyperemesis gravidarum that is generally seen. In women with twin and molar pregnancy which is associated with high HCG levels, HG is more common than normal pregnant women ²².

This result agrees with what of Derbent et al. ²³ stated that “Hyperemesis gravidarum is associated with elevated levels of HCG, and such changes are independent of serum indicators of thyroid and liver function”. This opens field for further studies for predication of hyperemesis gravidarum and its outcome.

Also, this agrees with what Peled et al. ²⁴ stated in a study investigatedthe effects of serious hyperemesis gravidarum on the triple test (alfafeto-protein, estriol, Human Chorionic Gonadotropin(hCG)) screening results, the study resulted in “An increase in HCG levels in patients with severe hyperemesis gravidarum affects the triple test screen results. When counseling patients about their overall risk of chromosomal abnormalities, this information should be taken into account.”

On the contrary,Derbent et al. ²³concluded that  no evidence of a link between high hCG levels and the development of HG. Also, there was no significant correlation between HG risk and HCG values ¹⁷.

There was no proven link between hCG values and HG in a retrospective cohort study of 4,372 pregnant women after in vitro fertilization²⁵.

The current study results showed there were no significant difference between cases with hospital stay< 4 days and cases with hospital stay ≥ 4 days was present as regard estradiol.

This is in agreement with Tan et al., ²²who stated that high estradiol level was not associated with prolonged stay or with more severe HG.Women with hyperemesis have increased estrogen levels than women without hyperemesis, according to another study²⁶.

The fact that people with HG have high estrogen levels in their blood suggests that estrogen plays a role in the disease's development. Furthermore, the negative effects of estrogen-containing birth control pills include nausea and vomiting. Estrogen lowers intestinal motility and slows gastric emptying, as well as causing fluid shifts that lower stomach acidity and promote H. pylori growth. Pregnant smokers have decreased estrogen levels and are more likely to get HG²⁷.

The fact that women with HG are more likely to suffer nausea while taking contraceptives with a mix of estrogen and progesterone supports a function for the two hormones ⁸. Total estradiol and HG studies, like hCG, are contradictory ¹⁸.

Estradiol can leads to nausea in non-pregnant women by disrupting the frequency and direction of stomach contractions. The reason of this disturbance is uncertain, but it is thought to be hormone signaling, which disrupts slow-wave stomach rhythms significantly. The potency of cholecystokinin (CCK) is increased by raising the sensitivity of vagal CCK type A receptors in the gut, which raises the potency of cholecystokinin (CCK). CCK reduces food intake by slowing stomach emptying and activating afferent neurons of the subdiaphragmatic vagal nerve.

²⁸.

CONCLUSION

Early-pregnancy hyperemesis gravidarum is a disorder highlighted by extreme vomiting,nausea, and anorexia, leading to dehydration and weight loss. There is a substantial association between HCG and hyperemesis gravidarum, no significant association between estradiol and hyperemesis gravidarum, and a substantial association between the presence of acetone and the severity of hyperemesis gravidarum, according to our findings. As a result, the higher the HCG levels, the more severe the hyperemesis gravidarum; ( i.e high levels of HCG increase the severity of HG).