Ovulation

7 – 9 days

“From the time a fertilized ovum enters the uterine cavity from the fallopian tube (which occurs 3-4 days after ovulation) until the time ovum implants (7-9 days after ovulation) the uterine secretions called uterinemilk provide nutrition for the early dividing ovum^“

“At the time of implantation, on days 21-22 of menstrual cycle the predominant morphologic feature is edema of the endometrial stroma.”

Important facts :

• Oogenesis begins in ovary at 6-8 weeks of gestation.°
• Maximum number of oocytes (6-7 million) are attained at 20 weeks of gestation.°
• All the primary oocytes in the ovary of a newborn are arrested In the late prophase (of meiosis) till puberty.°
• At puberty as a result of mid cycle preovulatory surge, meiosis is resumed and compTetedjust prior to ovulation.°
• Therefore first polar body is released just prior fo ovulation
• The second division starts immediately after_ it and is arrested in metaphase.°
• At the time of fertilization second division is completed which results in the release of oocyte and second polar body.
• Therefore second polar body release occurs only at the time of fertilisation.°
• LH surge preceedes ovulation by 34-36 hours.^o
• LH peak preceedes ovulation by 10-16 hours.^o
• Prior to ovulation :- Follicle reaches a size of 18-20mm.

                                    – Endometrium is 9-10 min trick.^o

                                    – Endometrium show triple line on USG.^o

• Ovulation occurs 14 days before the next menstruation.°
• Maximum action of corpus luteum is at 22 day of menstruation° (following which it starts regressing ~ 8 years after ovulation).°
• In absence of fertilisation and implanation the corpus leteum persists for 12-14 days.^o
• Maximum growth of corpus lutem of pregnancy is at 8th week of gestation and degenerates at 6  months of gestation.^o
• Fertilisation occurs in the ampullary part of fallopian tube.°
• Fertilised egg enters the uterus on day 18 – 19 of the cycle.°

Ans. is B. i.e. Accompanied by ovulation

26th day

• Ovulation is estimated to occur 14 days before the first day of succeeding cycle and this interval is fixed.
• In case of irregular cycles, it is the follicular phase which varies, but the luteal phase remains more or less constant at 14 days. therefore day of ovulation can be counted by counting 14 days backward.

As in the question a cycle of 40 days, ovulation will occur 14 days prior to next menstruation i.e. (40-14) = 26 day

Ans. is C. i.e. Mid-Cycle LH surge

Ans:A.)0.5 degree Fahrenheit.

• Before ovulation, there is only a small amount of progesterone present in your body and your basal body temperatures (your resting temperatures) are in the lower range.
• After ovulation, when there is increased progesterone secreted from the corpus luteum, temperatures become elevated.
• The temperature elevation that occurs after ovulation is sufficient to be measured with a BBT thermometer .
• The rise in temperature is usually about 0.4 degrees Fahrenheit or 0.2 degrees Celsius.

ls thick

9 days after ovulation

LH surge

LH surge

Ans:C.)36 Hours.

OVULATION

• It is the process by which the oocyte-cumulus is released from the follicle. 
•  A sustained peak level of estrogen for 24–36 hours in the late follicular phase → LH surge occurs from the anterior pituitary.
• Ovulation approximately occurs 16–24 hours after the LH surge. LH peak persists for about 24 hours. The LH surge stimulates completion of reduction division of the oocyte and initiates luteinization of the granulosa
• cells, synthesis of progesterone, and prostaglandins.

Ans. is D. All of the above

• Progesterone is secreted by the corpus luteum only after ovulation. Detection of progesterone or its metabolites can retrospectively confirm the occurrence of ovulation. Because progesterone causes a rise in basal body temperature (BBT), a measure of this temperature may also be useful for determining ovulation.
• LH Surge occurs 24-36 hours before ovulation.
• Most ovulation predictor kits work by measuring the level of luteinizing hormone (LH) in the woman’s urine – a rise in LH levels indicates that you are about to ovulate.
• Near the end of the first phase, estradiol levels peak, triggering the brain to release two hormones: a large surge of luteinizing hormone (LH), and a smaller surge of follicle-stimulating hormone (FSH). This then triggers ovulation. Just before ovulation, the follicle stops producing estradiol and its levels drop 

A and B both

Onset of the LH surge

Ans. is b i.e. Ovarian carcinoma  

Clinical Consequences of Persistent Anovulation

1. Infertility
2. Menstrual bleeding problems ranging from amenorrhea to irregular, heavy bleeding (DUB). The most common menstrual disorder associated with anovulation is oligomenorrhea.
3. Hirsutism, Alopecia and Acne.
4. Increased risk of Endometrial cancer and perhaps, Breast cancer.
5. Increased risk of Cardiovascular disease.
6. Increased risk of Diabetes mellitus in patients with insulin resistance.

Extra Edge :

Recommended investigations in case of anovulatory hyperandrogenic women (to exclude specific causes and problems).

In the presence of clinical signs of excess androgen stimulation – Two tests which should be done are :

1. Total testosterone levels
2. 17 – hydroxy progesterone morning and fasting.

Ans. is a and c i.e. Clomiphene citrate; and Tamoxifen

Drugs used for

• Clomiphene                                                                        • Chlorpromazine

(given 50mg daily OD from D2-D5 upto max. 150my/day)                 • Reserpine

• Tamoxifen                                                                           • Busulfan

(given 10mg BD from Day 2- Day 6 upto max. of 40mg daily)            • Vinca alkaloid

• Corticosteroid (Cortisone)                                                        • Bleomycin

useful in infertility d/t Congenital, adrenal hyperplasia,                     • Cytosine arabinoside

Addison’s disease                                                                        • Hydroxyurea

• Dexamethasone                                                                  • Electroconvulsive therapy

In patients of hirsutism (Dexamethasone + clomiphene                   • Estrogens/OCP’s

0.5mg at bed time), given good response                                       • Androgens

• Gonadotrophins                                                                    • Danazol

useful in cases where ovulation is arrested d/t failure in the production of gonadotrophins by the HPO axis

Available preparation : HMG (has 75U of FSH & LH each) Purified urinary FSH

Recombinant FSH

Recombinant HCG

Recombinant LH

• GnRH (In cases where anovulation occurs d/t hypothalamic inhibition with anterior pituitary intact), GnRH analogues are used to induce ovulation.

• Bromocriptine It does not Specifically induce ovulation but is DOC for those women with dysmenorrhea / infertility associated with hyperprolactinemia.

Ans.is D.)All i.e: Minipill (progesterone only pill); IUCD; and Norplant

• Norplant offers long-term contraception through the use of subdermal capsules filled with levonorgestrel. The six capsules are implanted in the inside part of the upper arm. The levonorgestrel is released from the capsules gradually, providing contraception for about 5 years. The primary mechanism of action of Norplant is suppression of ovulation.
• IUCDs primarily work by preventing fertilization.The progestogen released from the hormonal IUDs may prevent ovulation from occurring but only partially.The hormone also thickens the cervical mucus so that sperm cannot reach the fallopian tubes. Copper IUDs contain no hormones, but the copper ions in the cervical mucus are toxic to sperm. They also cause the uterus and fallopian tubes to produce a fluid that contains white blood cells, copper ions, enzymes, and prostaglandins, a combination that is also toxic to sperm.
• Mechanism of Action of Mini pill(Progesterone Containing pill):Progestin-only oral contraceptives – Mechanisms of action include (1) suppression of ovulation; (2) a variable dampening effect on the midcycle peaks of LH and FSH; (3) an increase in cervical mucus viscosity; (4) a reduction in the number and size of endometrial glands; and (5) a reduction in cilia motility in the fallopian tube

Ans is C. i.e. Hysteroscopy 

METHODS TO DOCUMENT OVULATION:

• Luteinizing Hormone Monitoring Documentation of the LH surge represents a remarkably reproducible method of predicting ovulation. 
• Ovulation occurs 34 to 36 hours after the onset of the LH surge and about 10 to 12 hours after the LH peak.
• Basal Body Temperature The least expensive method of confirming ovulation is for the patient to record her temperature each morning on a basal body temperature (BBT) chart.
• Midluteal Serum Progesterone
• Ultrasound Monitoring Ovulation can also be documented by monitoring the development of a dominant follicle by ultrasound until ovulation takes place.
• A ferning pattern is seen when periovulatory cervical mucus is spread and dried on a microscope slide.

Cervical mucous

REF: Shaw 13th ed p. 213

“Cervical mucus changes can be used to assess ovulation using the fern test”

Ans. is b i.e. 7 – 9 days

“From the time a fertilized ovum enters the uterine cavity from the fallopian tube (which occurs 3-4 days after ovulation) until the time ovum implants (7-9 days after ovulation) the uterine secretions called uterine milk provides nutrition for the early dividing ovum.”

“At the time of implantation, on days 21-22 of menstrual cycle the predominant morphologic feature is edema of the endometrial stroma.”

Important facts :

• Oogenesis begins in ovary at 6-8 weeks of gestation.°
• Maximum number of oocytes (6-7 million) are attained at ‘in weekF• of gestation.°

•

All the primary oocytes in the ovary of a newborn are arrested in the late prophase (of meiosis) till puberty.°

• At puberty as a result of mid cycle preovulatory surge, meiosis is resumed and completed just prior to ovulation.°
• Therefore first polar body is released just j.-,r,or to °mistier..
• The second division starts immediately after it and is arrested in metaphase.Q
• At the time of fertilization second division is completed which results in the release of oocyte and second polar body.
• Therefore second polar body release occurs only at the time of fertilisation.°

LH surge precedes ovulation by 34-36 hours.°

• LH peak precedes ovulation by 10-16 hours.°
• Prior to ovulation : – Follicle reaches a size of 18-20 mm.

–     Endometrium is 9 – 10 mm thick.°

–     Endometrium shows triple line on USG.°

• Ovulation occurs 14 days before the next menstruation.°
• Maximum action of corpus luteum is at 22 day of menstruation° (following which it starts regressing – 8 days after ovulation).°
• In absence of fertilisation and implantation the corpus luteum persists for 12 – 14 days.°
• Maximum growth of corpus luteum of pregnancy is at 8th week of gestation and degenerates at 6 months of gestation.°
• Fertilisation occurs in the ampullary part of fallopian tube.°
• Fertilised egg enters the uterus on day 18 – 19 of the cycle.°

18-21

Ans:C. 24-36 hrs

• A sustained peak level of estrogen for 24–36 hours in the late follicular phase → LH surge occurs from the anterior pituitary.
• Ovulation approximately occurs 16–24 hours after the LH surge.
• LH peak persists for about 24 hours.
• The LH surge stimulates completion of reduction division of the oocyte and initiates luteinization of the granulosa cells, synthesis of progesterone and prostaglandins.

The fate of the corpus luteum depends on whether a pregnancy occurs.

Following the LH surge, the corpus luteum is programmed to secrete progesterone for 10–12 days.

Without further LH stimulation and in the absence of pregnancy, both major cell types of the corpus luteum cease steroid production and undergo apoptosis while the tissue regresses. The corpus luteum that persists for part of only one menstrual cycle is called a corpus luteum of menstruation.

Following ovulation, the corpus luteum develops from the remains of the dominant or Graafian follicle in a process referred to as luteinization. The human corpus luteum is a transient endocrine organ that, in the absence of pregnancy, will rapidly regress 9 to 11 days after ovulation.

Luteolysis results from decreased levels of circulating LH in the late luteal phase and decreased LH sensitivity of luteal cells. Luteolysis is characterized by a loss of luteal cells by apoptotic cell death.

The finding of secretory endometrium confirms ovulation.

The use of an endometrial biopsy (EMB) near the end of the luteal phase can provide reassurance of an adequate maturational effect on the endometrial lining.

Within 48 hours of ovulation, the cervical mucus changes under the influence of progesterone to become thick, tacky, and cellular, with loss of the crystalline fernlike pattern on drying.

The best method of assessment of female fertility that allows accurate prediction of ovulation is the measurement of urinary LH surge (Hormonal Test).

WHO classification of disorder of ovulation is given below Type I – Hypogonadotropic hypogonadism, low FSH and LH, low oestradiol Type II – Normogonadotropic hypogonadism, normal FSH, normal oestradiol Type III – Hypergonadotropic hypogonadism, high FSH and LH, low oestradiol

Ref: Essentials of Gynaecology by Lakshmi Seshadri, Edition 1, page – 274.

Estrogen makes the mucus much thinner and more alkaline, changes that promote the survival and transport of sperm.

Progesterone makes it thick, tenacious, and cellular.

The mucus is thinnest at the time of ovulation, and its elasticity, or spinnbarkeit, increases so that by midcycle a drop can be stretched into a long, thin thread that may be 8–12 cm or more in length.

Ovulation occurs due to the effect of increased concentration of LH. In the pre-ovulatory phase of the menstrual cycle, the ovarian follicle will undergo a series of transformations called cumulus expansion, which is stimulated by FSH. This is followed by LH surge.

The fertilised ovum takes 3-4 days to travel through the fallopian tube and reaches the uterine cavity by the 7th day from ovulation. It is fully embedded in the endometrium by the 14th day.

D i.e. Progesterone

Progesterone is thermogenic & responsible for the rise in basal body temperatureQ at the time of ovulation

• Increase in basal body temperature at the time ovulation in reliable indicator of time of ovulation The rise starts 1-2 days after ovulation
• Other indicators of ovulation

– Secretory patternQ on biopsy of endometrium

– Thick cervical mucus that forms a fern pattern

Ans. is ‘b’ i.e., Inhibition of ovulation

Mechanism of action of OCPs

Inihibition of gonadotropin release from pitutary by reinforcement of normal feedback inhibition —> No prevulatory LH surge —> No ovulation

This is the most important mechanism.

1. Thickening of cervical mucus secretion (due to progesterone)       hostile to sperm penetration.
2. Even if ovulation and fertilization occur, the blastocyte fails to implant because endometrium is either hyperproliferative or hypersecretory – not suitable for nidation                                          
3. Important in case of postcoital pill.
4. Uterine and tubal contractions may be modified to disfavour fertilization.
5. Postcoital pills may dislodge a just implated blastocyte or may interfere fertilization/implantation.

Ans. B: Ovulation

The remaining daughter cells generated from the meiotic events contain relatively little cytoplasm and are referred to as polar bodies. Eventually, the polar bodies degenerate.

There may be one or two polar bodies in the ovum. The first polar body is one of the two products in the first stage of meiosis, just before ovulation and is considered diploid, with 23 duplicated chromosomes. The second polar body is haploid, with 23 unduplicated chromosomes and is produced only when a sperm penetrates the oocyte.

Ans. D: Fall in body temperature

Frequent physical signs indicating ovulation are:

• Increased body temperature
• LH surge
• Increased cervical mucus -cervical mucus is most abundant and becomes clear and slippery and stretches like egg white
• Change of position and firmness of cervix
• Abdominal cramps (Mittelschmerz)
• Increased libido
• Tender breasts

Ans. B: 14 days prior to next menstruation

In the follicular (pre-ovulatory) phase of the menstrual cycle, the ovarian follicle will undergo a series of transformations called cumulus expansion, this is stimulated by the secretion of FSH. After this is done, a hole called the stigma will form in the follicle, and the ovum will leave the follicle through this hole.

Ovulation is triggered by a spike in the amount of FSH and LH released from the pituitary gland. During the luteal (post­ovulatory) phase, the ovum will travel through the fallopian tube toward the uterus.

If fertilized by a sperm, it may perform implantation there 6-12 days later.

In humans, the few days near ovulation constitute the fertile phase.

The average time of ovulation is the fourteenth day of an average length (twenty-eight day) menstrual cycle.

It is normal for the day of ovulation to vary from the average, with ovulation anywhere between the tenth and nineteenth day being common, but commonly occurs 14 days before the next cycle.

Cycle length alone is not a reliable indicator of the day of ovulation.

Ans. B: 4 weeks

In non-lactating mothers, ovulation may occur as early as 4 weeks and in lactating mothers about 10 weeks after delivery

Ans. B i.e. Urine FSH

Physiology

• The best predictor of ovulation: Pre-ovulatory rise in LH
• In the normal menstrual cycle, progesterone is secreted by Corpus luteum
• Inhibin is secreted by Graffian follicle
• LH precedes ovulation by 24 hours (Ovulation coincides with LH surge)
• Ovulatory period: Corresponds to 14 days before next menstruation
• FSH stimulates: Growth of granulosa cells (a measure of ovarian reserve)
• LH stimulates Follicle rupture and ovulation.

Ans. is ‘a’ i.e., 1-2 days

Ans. is ‘b’ i.e., 5-7

Ans. is ‘b’ i.e., Before ovulation