Fellowship in Reproductive Medicine: Physiological Changes in Early Pregnancy

 

Physiological changes in early pregnancy. What are our learning objectives? What is the importance of physiological changes during pregnancy? And to discuss in detail about the important changes in reproductive system and various other systems in pregnancy. The importance is that during pregnancy, the pregnant mother undergoes significant anatomical and physiological changes in order to nurture and accommodate the developing fetus.

The changes begin to occur early in the first trimester, peaking at term and revert to pre-pregnancy levels by six weeks into the puerperium. Unless well understood, these physiological adaptations of normal pregnancy can be misinterpreted as pathological. Now, what could be the changes in the various systems in pregnancy? It could be the genital organs, the breast, hematological, cardiovascular, respiratory, renal, endocrine, and gastrointestinal.

Let's talk of the genital organs first. The vulva and the vagina, both become edematous and vascular. With the vulva, we have the superficial varicosities, especially in the multipara.

The labia minora gets pigmented and hypertrophied. With the vagina, you have a hypertrophied wall, bluish discoloration of the mucosa, which is also known as the jacamas sign, secretions which are copious, thin, and acidic pH of 3.5 to 6. What about the cervix? In early pregnancy, changes takes place in the position and texture of the cervix and the consistency and color of the cervical discharge. If she has conceived, the cervix will feel softer, more closely resembling the texture of the lips, hypertrophy and hyperplasia of the elastic and connective tissues.

Vascularity is increased, softening of the cervix resembling the lips is the Goodell sign, and squamous cells also become hyperactive. Also, in addition, estradiol and progesterone makes the cervix swollen and softer during pregnancy. Estradiol, in addition, stimulates growth of columnar epithelium of the cervical canal, which also can be seen as an ectropion, visible part of the ectocervix, prone to contact bleeding.

It appears bluer because of the vascularity. Distended mucous glands result in increased complexity, production, thickening mucus, operculum, and, of course, the protective plug. The cervix softens as a result of remodeling of the cervical collagen and the leukocytes' collagenase.

Let's now discuss the uterus itself. What effects do estrogen and progesterone have on the uterus? Increased uterine growth and enlargement, hypertrophy and hyperplasia of muscle fibers, a noticeable increase in length and width up to 12 weeks, three separate layers of muscle fibers—intermediate, inner circular, and outer longitudinal—the apposition of two double-curved muscle fibers, and a figure of eight are all present. When muscles contract, they function as live ligatures in addition to blocking blood arteries.

How does pregnancy affect the uterus's position, size, and shape? At first, the corpus and fundus are pear-shaped organs, but as pregnancy goes on, they start to seem more globular. By 12 weeks, the uterus is nearly spherical. The uterus subsequently takes on an oval shape and quickly becomes longer than wide.

The rectosigmoid, which is on the left side, typically causes the uterus to dextrorotate as it ascends from the pelvis. As a result, the uterus is shifting to the right. What changes may the breasts be undergoing? fat accumulation surrounding the glandular tissue.

The growth of ducts is significantly accelerated by estrogen. Hypoprolactinemia and progesterone stimulate the alveolar glands. Vascularity is elevated. The size, erectility, and deep pigmentation of the breasts increase. Montgomery's Tubercles is another name for the hypertrophied sebaceous glands that occur in varying numbers. Nevertheless, estrogen counteracts the increased prolactin during pregnancy, so you won't produce any milk.

Therefore, the first pregnancy is when breast alterations are most noticeable. Now, what may be the hematological changes? This is crucial to comprehend. Estrogen and progesterone levels rise during pregnancy, which directly affects the kidneys, triggering the release of renin, activating the aldosterone renin angiotensin mechanism, renal sodium retention, an increase in total body water, a 45% increase in blood volume, and physiological anemia.

All this leads to adequate perfusion of vital organs including placenta and fetus to anticipate blood loss associated with delivery and these hematological changes tend to amount to almost a 50% increase in the blood volume, which again, as we go into the next slide, we will see that the RBC mass increases by 20% and due to the increase in renal erythropoietin production and supports higher metabolic requirements for oxygen during pregnancy. What happens to the blood components like the WBC? It's mainly due to the increase in the number of the peripheral mononuclear sites as early as three weeks into pregnancy. It's difficult to differentiate with infection and therefore you see a neutrophilia in the blood.

How about the platelets? However, there is a decrease to low normal levels due to increased platelet consumption, and moderate thrombocytopenia may be observed during pregnancy. Let's examine the potential cardiovascular alterations that may occur during pregnancy. A 15%–20% increase in heart rate, a 30% increase in stroke volume, a nearly 50% increase in cardiac output, and a decrease in blood pressure followed by an increase.

This happens because the blood volume is increased and there is also a drop in blood pressure and an increase later on. What about the respiratory changes? Indeed, the estrogen effect, capillary engorgement of the nasal, oropharyngeal, and laryngeal mucosa, and an increase of 2 cm in the anterior-posterior and transfer diameter of the chest wall, along with a corresponding increase of 5 to 7 cm in circumference, could all be the cause. This would result in a 25% increase in expiratory reserve volume and a 15% increase in inspiratory capacity.

So you will see that there has been variations in the respiratory changes because the diaphragm tends to hinge upward because of the pregnancy.

What about the ventilation and oxygenation as a result of this? Increase in ventilation begins around the 8th week of gestation, most likely in response to progesterone-related sensitization of the respiratory center to carbon dioxide and increase in the metabolic rate. This then leads to changes in mechanical aspects of ventilation. It increases the tidal volume by 50% from 500 to 700 ml, reduction in functional residual capacity and the thoracic anatomy changes because of the elevation of the diaphragm by the enlarging uterus and reconfiguration of the chest wall, change in lung volume and increase in pulmonary blood flow.

Mild fully compensated respiratory alkalosis is therefore normal in pregnancy. What could be the renal changes? First, let's study the anatomy. There is an increase in length of about 1 to 2 cm of the kidney.

The calyces, renal pelvis and ureters dilated. Impression of obstruction. Anatomical changes predispose pregnant women to ascending UTI.

By 6 weeks postpartum, renal dimensions return to pre-pregnancy values. As a result of these anatomical changes, what could be the functional changes? Renal vascular resistance decreases. Renal plasma flow increases 50 to 85% above non-pregnant values during first half of pregnancy.

Renal perfusion increases, rise in GFR by approximately 50%. Glomerular filtration rate returns to normal within 12 weeks of delivery and renal clearance of creatinine increases as the GFR rises. The endocrine changes, as we can see here, is rather a busy slide.

You'll see that the HCG is there and the alpha and beta, which is the beta is this pregnancy specific, which is produced by the trophoblast and is required for the implantation. Now the human placental lactogen, which is again produced by the placenta, partial homology with the prolactin and the human growth hormone. We also have steroids and we have estrogen and progesterone.

So you will see in this slide what goes up and what goes down. So there is a lot of interplay between a lot of hormones over here and therefore complex changes with hormones are known to take place in pregnancy. What about the pituitary gland? It's known to be the master gland of the body and the anterior lobe has the growth hormone production is decreased, but the serum growth hormone levels are increased due to growth hormone from the placenta.

Serum prolactin levels increase in the first trimester and are 10 times higher at term. FSH levels and LH levels are undetectable, but let's look at the prolactin levels here. Due to increasing serum estradiol concentrations during pregnancy, the milk secretion is suppressed and then because of the drop in the estradiol levels, you will find that the let down reflex will allow for milk flow after delivery.

The negative feedback from the levels in the estrogen, progesterone and inhibin make the FSH and LH levels undetectable. So with the posterior pituitary, which actually gives the oxytocin and the vasopressin, oxytocin levels increase in pregnancy and peak at term. Levels of the antidiuretic hormone remain unchanged.

The carbohydrate metabolism is extremely important because you have the insulin secreting pancreatic beta cells undergo hyperplasia, resulting in increased insulin secretion and increased insulin sensitivity in early pregnancy, followed by progressive insulin resistance begins in the second trimester and peaks in the third trimester. Pregnancy we know is a diabetogenic state. Due to increasing secretion of diabetogenic hormones like placental lactogen, growth hormone, progesterone, cortisol and prolactin, this again leads to progressive insulin resistance beginning in the second trimester and peaks in the third trimester.

Now, because pregnancy is a diabetogenic state, it also allows for shunting of glucose to the fetus to promote development while maintaining adequate maternal nutrition. Now, it's an important function is the thyroid. Physiological changes of pregnancy cause the thyroid gland to increase production of thyroid hormones by 40-100% to meet maternal and fetal needs.

Moderate enlargement during pregnancy cause a glandular hyperplasia and increased vascularity. The fetal thyroid starts functioning from the 12th week of gestation up to the fetus is dependent on the placental transmission of thyroxin for its development. So, early in the first trimester levels of carrier protein thyroxin binding globulin increases thus bound to T3 and T4 increase, but do not affect serum-free T4 and T3 levels.

And normal suppression of TSH during pregnancy may lead to a misdiagnosis of subclinical hyperthyroidism. If we look at this, the HCG and the TSH, HCG is maximal and it can suppress maternal TSH production in the first trimester. HCG or TSH may result in nausea and vomiting and improve after first trimester.

The biochemical hyperthyroidism is perhaps because of increased free thyroxin and suppressed TSH that may cause hyperemesis gravidarum, iodine active transport to fetal placental unit and increased urine excretion and plasma level drops, therefore increased uptake of iodine from blood by the thyroid gland. Free T4 and T3 fall a little in the trimester of 2nd and 3rd. What about the gastrointestinal and the hepatobiliary system? When there is an increase in progesterone levels as the pregnancy advances, increased placental production of gastrin which increases the gastric acidity that is the heartburn, reduces motility of the gut which results in delay of the gastric emptying time and causes constipation and the lower gastroesophageal sphincter tone to be reduced which can again cause an esophageal reflux.

Liver and gallbladder are the other two organs which also has to be noted. No histological changes in liver cells with the exception of a raised alkaline phosphatase. Other liver function tests are unchanged.

Hepatic production of protein increases but serum albumin levels still remain low. Increase in production of plasma fibrinogen and the clotting factors, mild cholestates, marked atonicity of the gallbladder which is a progesterone effect. This impairment leads to stasis and is associated with the increased cholesterol saturation of pregnancy.

So, with gastrointestinal symptoms associated with pregnancy, constipation, morning sickness, gastroesophageal reflux and hemorrhoids can be noted. So, if we had to look at the summary, we have talked about the nervous system, immune system, mammary gland, liver, digestive tract, bone, skeletal muscles, respiratory systems, cardiovascular system, hematological systems, spleen, renal system, pancreas and of course, the adipose tissue. And with all the systems having been involved and the changes, I am sure you will realize that pregnancy is not simple.

One has to look at the pregnant mother with a lot of respect because all the systems in the body get changed to an extent that sometimes the morbidity could be high if we sort of not look at all the systems in pregnancy with the physiological changes of pregnancy, because otherwise we may treat them as pathological and that could cause problems.

Under the direction of Padma Shri Dr. Kamini Rao, Medline Academics has been offering a number of basic and advanced courses in reproductive medicine to students for many years, and it remains the most sought-after medical program in reproductive medicine. One of the best fellowship programs in the nation is offered by the Fellowship in Reproductive Medicine (FRM) and the Fellowship in Embryology (FIE), which offer a hybrid mode of education. Students can attend all online modules at their convenience, while weekly classes through the Live Contact Program cover nearly all of the most sought-after topics in the field. Before students can handle real patients, they must finish their simulation training at a centre in Bangalore that has world-class simulation training facilities. It features the best simulation training and top-notch training tools available at this training facility.

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