Patient's question:
How to regulate luteal phase insufficiency? Thank youDoctor's answer:
Luteal phase defect (LPD) refers to insufficient progesterone secretion or premature luteal regression, leading to inadequate secretion of the endometrium, which results in difficulties in implantation of the zygote or early pregnancy miscarriage. The exact factors or causes are still unclear. It may be related to insufficient luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion by the pituitary gland, excessive or insufficient prolactin secretion by the pituitary gland, immaturity of the follicle itself and insensitivity to gonadotropins, insufficient ability of the corpus luteum to synthesize progesterone, or an imbalance in the ratio of estrogen to progesterone.[Definition] Luteal phase defect (LPD) is a syndrome characterized by incomplete luteal development and function, insufficient progesterone secretion, inadequate endometrial secretion, and menstrual disorders. The natural incidence of this condition in women of reproductive age is 5%, with an incidence of 3.5%-10% in infertility cases and 35% in early pregnancy miscarriages, and 4%-60% in habitual abortions.
[Etiology and Pathology] Under normal conditions, after ovulation, the follicle undergoes luteinization to form the corpus luteum, which secretes estrogen and progesterone. The secretion peaks 7-8 days after ovulation and then rapidly declines 1-2 days before menstruation. If there is insufficient secretion of gonadotropins and estrogen by the pituitary gland, follicular development will be incomplete, and although the ovary can ovulate, the corpus luteum development is often affected, leading to luteal phase defect. Currently, it is generally believed that LPD is related to the following factors:
1. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis: Abnormal release rhythm or amplitude of gonadotropin-releasing hormone (GnRH) leads to abnormal secretion of pituitary gonadotropins FSH and LH.
2. Abnormal rhythms and ratios: Such as insufficient FSH secretion leading to poor follicular development, hypersecretion of high-tension LH, low LH peak during ovulation, abnormal secretion of inhibin, insufficient LH secretion during the luteal phase, and desynchronization of histological changes and sex hormone secretion timing in the endometrium.
3. Abnormal endocrine function of the uterus: Such as reduced ratio of prostaglandin I2/TXA2.
4. Hyperprolactinemia (HPRL): It has been reported that about 70% of LPD cases are combined with HPRL. Prolactin (PRL) participates in the regulation of the pulse frequency and amplitude intensity of LH release through paracrine mechanisms, affecting the enzyme system function of ovarian progesterone synthesis.
5. Iatrogenic factors: Including anti-estrogens (CC), synthetic progestins (medroxyprogesterone acetate), and prostaglandins (PG). Clinical observations have found that the incidence of LPD during CC ovulation induction treatment is 29%-50%. The mechanism by which CC induces LPD is not yet fully understood. It is observed that it is related to the following aspects:
1) CC inhibits the secretion of progesterone by ovarian granulosa cells in a dose-dependent manner but does not change the activity of 3β-hydroxysteroid dehydrogenase or the utilization of pregnenolone.
2) CC directly affects the responsiveness of the endometrium to progesterone, resulting in desynchronization between the endometrium and progesterone, known as ectopic endometrium (OOP). The incidence of OOP is 24%-85%, and it is not conducive to the implantation of the zygote and the development of the embryo.
3) CC causes abnormal content and function of estrogen receptor (ER) and progesterone receptor (PR) in the endometrium. The mechanism is that the anti-estrogenic effect of CC hinders the production of ER and leads to a decline in PR function, similarly causing incomplete endometrial development and desynchronization. However, some observations suggest that CC does not affect the content and function of ER and PR in the endometrium. Synthetic progestins such as medroxyprogesterone acetate and prostaglandins can cause luteolysis and premature atrophy of the corpus luteum.
[Clinical Manifestations] LPD is divided into two types based on its developmental phase and progesterone secretion characteristics:
1. Luteal phase defect: This refers to premature regression and atrophy of the corpus luteum. The normal lifespan of the corpus luteum is 14±2 days. If the luteal phase is less than 10 days, it can lead to frequent menstruation, shortened cycles, bleeding before menstruation, excessive menstrual bleeding, infertility, and early pregnancy miscarriage. The pathological changes in the endometrium are irregular maturation or incomplete secretion.
2. Incomplete luteal regression: This refers to a luteal phase longer than 14 days and the inability to completely regress within 3-5 days, resulting in continuous progesterone secretion and incomplete shedding of the endometrium. Clinical manifestations include bleeding before menstruation, prolonged menstruation, excessive menstrual bleeding, prolonged bleeding, and anemia. This type can also be combined with luteal phase defect.
[Medical Opinion and Treatment Principles] Due to luteal phase defect, women are unable to produce sufficient progesterone, reducing the chances of conception. Even if conception occurs, the insufficient corpus luteum may prevent the normal implantation of the zygote, making it one of the causes of infertility and habitual abortion in women. Clinical observations have found that women with anovulation, ovarian cysts, positive anti-sperm antibodies, and blood deficiency-related tubal adhesions all exhibit clinical manifestations of luteal phase defect. Therefore, by eliminating the obstacles of luteal phase defect in women, many diseases can be excluded. Here, I will introduce the role of the corpus luteum in women's menstrual cycle: The corpus luteum forms and regresses with the cyclical changes of the ovary, including the development, maturation, and ovulation of the follicle. As the follicle develops and matures, it gradually moves towards the surface of the ovary, forming a bubble-like protrusion. It is influenced by pituitary hormones and proteolytic enzymes, leading to the rupture of the follicular membrane and the release of follicular fluid. At this time, the oocyte and its surrounding granulosa cells are also expelled into the abdominal cavity. This process is called ovulation. The oocyte that leaves the ovary is called the ovum. Women with relatively regular menstrual cycles experience ovulation between two menstrual periods. Ovulation can occur alternately between the two ovaries or cyclically in one ovary. Generally, only one ovum matures per cycle, although occasionally two may mature. After being expelled, the ovum enters the fallopian tube. If it encounters sperm, it can be fertilized to form a zygote. Otherwise, the oocyte can be absorbed or regress on its own.
Formation and regression of the corpus luteum: After ovulation, the in the ovary closes. Due to the rupture of blood vessels in the follicular membrane, blood leaks into the cavity and forms a blood clot, creating a corpus luteum (early corpus luteum). The broken in the follicular wall is quickly sealed by fibrin, leaving behind the granulosa cells on the follicular wall, which rapidly proliferate and enlarge under the action of luteinizing hormone. At this time, yellow granules appear in the cytoplasm, called granulosa lutein cells. Some follicular membrane cells also undergo luteinization, hence the name theca lutein cells. Subsequently, connective tissue and capillaries around the corpus luteum proliferate and extend into the blood clot at the center of the corpus luteum, forming partitions, giving the corpus luteum a mottled appearance. At this stage, the unfertilized follicle begins to atrophy. The corpus luteum reaches full development 8-9 days after ovulation, with a diameter of 1-3 cm, and is called the mature corpus luteum. If the oocyte is fertilized, the corpus luteum can maintain its function for 3-4 months before regressing, called the pregnant corpus luteum. If the oocyte is not fertilized, the corpus luteum begins to regress, with reduced blood vessels and cell atrophy, the yellow color fades, and the secretion function declines. Menstruation can occur 4-6 days later. At this time, the ovary starts to develop a new follicle, forming a new cycle.
Clinically, Western medicine divides the disorders in the formation and regression of the corpus luteum into two cases: luteal phase defect and incomplete luteal regression. We say that the normal luteal phase is 12-16 days. Women with luteal phase defect have a luteal phase shorter than 9-11 days or a normal luteal phase length but insufficient function, with a basal body temperature rise of less than 0.5 degrees, indicating lower progesterone secretion. As a result of luteal phase defect and premature regression of the corpus luteum, the endometrium peels off prematurely. Clinical manifestations include spotting before menstruation, early menstrual onset, varying menstrual volume, early abortion, habitual abortion, and infertility. Due to insufficient progesterone secretion by an underdeveloped corpus luteum, the endometrium before menstruation remains in the early secretory stage with poor secretion response, and the endometrium has slight bending, making it difficult to conceive. Women with luteal phase defect, due to the corpus luteum not atrophying and regressing on time or not completely regressing, continue to secrete a small amount of progesterone, preventing the endometrium from shedding at the normal time. Clinical manifestations include normal menstrual cycles but prolonged menstruation, lasting 9-10 days or even longer, with moderate menstrual volume, biphasic basal body temperature, but only declining during menstruation. For the treatment of this disease, Western medicine often uses hormone therapy, such as progesterone and human chorionic gonadotropin. Here, I will focus on the treatment methods of traditional Chinese medicine:
From clinical observations, women with luteal phase defect all have symptoms of spleen and kidney deficiency. Traditional Chinese medicine believes that the kidney governs closure and storage. If there is a deficiency of kidney qi in the body or irregular sexual activity that damages the, leading to the inability to maintain kidney qi and the loss of its function in closure and storage, resulting in dysfunction of the and abnormal accumulation and discharge of blood, leading to menstrual disorders. Therefore, women with luteal phase defect, due to insufficient kidney yang, may have pale complexion, low spirits, sore waist and knees, dizziness, loose stools, pale tongue with white coating, and deep and thready pulse, especially in the two lower limbs. Due to insufficient kidney qi and the inability to stabilize the, there may be spotting before menstruation or prolonged menstruation, thin leukorrhea, and easy fetal leakage. At the same time, due to insufficient yang qi, there may be low spirits. Due to yang qi deficiency, there may be aversion to cold and cold limbs. Due to prolonged bleeding, there may be dizziness. Due to the decline of the fire, there may be clear and long urine. At the same time, traditional Chinese medicine points out that whether the uterus can normally menstruate and nurture the fetus depends on the of the, and the of the depends on the kidneys. If the kidney function is vigorous, then the will also be vigorous, and women will be able to have normal menstrual cycles and conceive. Therefore, in the treatment, it is appropriate to use the method of tonifying the kidney and consolidating closure. Among the thousands of infertile patients treated, 25% were infertile due to luteal phase defect, and they generally achieved pregnancy after about 3 months of treatment. Another 5% had habitual abortion, and after treatment, they could give birth to full-term healthy infants.
I am from the Family Planning Commission's infertility department. We offer comprehensive package pricing for the treatment of male and female infertility, with experienced medical experts signing agreements to ensure pregnancy. Many women get pregnant in the same month, but the key is to be able to treat and cure the disease, which is the true expertise!