(PROF.) DR. SRIMANTA KUMAR PAL (SENIOR GYNECOLOGIST): Tips from Dr. S K Pal For Ovulation induction

1) General Information on PCOS : 2) Minimal Evaluations 3) Monitoring...4) CC 5) All protocols, 3) Types of gonadotropins, 4) selection of dose of gonadotropins., 5) IUI

6) Agonists & Antagonists in IUI cycles .7) Recagon Pure FSH. : Pretreatment with OCP and then induction.

8) LPD

9) P supplementatio 9) IVF 10)Poor Responders. 12) IVM. 11)Ovarian insufficiency

12) Endomterial Receptive & Thin EndometriumFollicle Monitoring... 2) Gonadototrophins.-All protocols, 3) Types of gonadotropins, 4) selection of dose of gonadotropins., 5) IUI

6) Agonists & Antagonists in IUI cycles .7) Recagon Pure FSH.

8) LPD 9) IVF 12) IVM.

9) P supplementation 10)Poor Responders 12) Life style modification, Caloric restriction ,& Physical Exercise are most important initial step. 11)Ovarian insufficiency. 12) Life style modification, Caloric restriction, & Physical Exercise are most important initial step. 13) Trouble shooting in OI.

A)GENERAL INFORMATIONS ON PCOS & OVULATION INDUCTION.

Of al anovulatory infertility PCOS is the causation in 80% of cases. Life style modification, Caloric restriction, & Physical Exercise are most important initial step.

B) CYCLE/ FOLLICLE MONITORING

Basal Scan, Day 3 hormones, Follicular phase E2, Progesterone, initiation of TVS, Commencement of LH urine kit and Trigger, Estimation of Luteal phase length, Serum E2 & P in midluteal phase.

Where TI/Natural Cycle IUI may be tried? This is relevant where there is a real risk of OHSS. But women who areal owe for natural cycle IUI. Or even TI are cases who are endocrinologically normal-no PRL,Androgen disorders & Euthyrpoid.If in previous cycle the Luteal phase length is normal then & normal midluteal E2 and OP are normal then natural cycle IUI may be tried or TIN may be tried.ily monitoring thereafter.

Basal Scan:-Day 3 scan:-

Serum E2 in Follicular phase:-in a mature follicle the level should be > 150-200 pg/ml.

TVS –How often? It should be commenced from Day 10 and then daily.

Urinary LH Kit: - Once a follicle has attained 17 mm in size then twice daily serial Urine testing is done. If serum LH is> 10 IU /Lit in otherwise normal women it implies that surge has commenced.

Sonological signs of ovulation:-

C) CYCLE/ FOLLICLE MONITORING

Basal Scan, Day 3 hormones, Follicular phase E2, Progesterone, initiation of TVS, Commencement of LH urine kit and Trigger, Estimation of Luteal phase length, Serum E2 & P in midluteal phase.

Basal Scan:-Day 3 scan:-

Serum E2 in Follicular phase:-in a mature follicle the level should be > 150-200 pg/ml.

TVS –How often? It should be commenced from Day 10 and then daily.

Sonological signs of ovulation:-

A) CYCLE/ FOLLICLE MONITORING

Basal Scan, Day 3 hormones, Follicular phase E2, Progesterone, initiation of TVS, Commencement of LH urine kit and Trigger, Estimation of Luteal phase length, Serum E2 & P in midluteal phase.

Basal Scan:-Day 3 scan:-

Serum E2 in Follicular phase:-in a mature follicle the level should be > 150-200 pg/ml.

TVS –How often? It should be commenced from Day 10 and then daily.

Sonological signs of ovulation:-

1A. Clomiphen Citrate.

• PCOS

• In patients with PCOS, ovulation is induced either with the use of pharmaceutical compounds, or the application of other methods, such as weight loss and exercise, or laparoscopic ovarian drilling. Antiestrogens and human gonadotrophins are common agents, while pulsatile GnRH and GnRH agonists are hardly used today. Recently, GnRH antagonists have been introduced, while insulin sensitizers and aromatase inhibitors are also currently employed.

· PROLACTIN

· Elevations in prolactin may cause amenorrhea or galactorrhea. Amenorrhea with-out galactorrhea is associated with hyperprolactinemia in approximately 15% of women.

In patients with both galactorrhea and amenorrhea, approximately two-thirds will have hyperprolactinemia; of those, approximately one-third will have a pituitary adenoma. In more than one-third of women with hyperprolactinemia, a radiologic abnormality consistent with a microadenoma (> 1cm) is found

1A.

The ovarian hyperstimulation syndrome (OHSS) has been reported to occur in patients receiving

Clomiphene citrate therapy for ovulation induction. In some cases, OHSS occurred following

cyclic use of clomiphene citrate therapy or when clomiphene citrate was used in combination

with gonadotropins. Transient liver function test abnormalities suggestive of hepatic dysfunction,

which may be accompanied by morphologic changes on liver biopsy, have been reported in

association with ovarian hyperstimulation syndrome (OHSS).

OHSS is a medical event distinct from uncomplicated ovarian enlargement. The clinical signs of

this syndrome in severe cases can include gross ovarian enlargement, gastrointestinal symptoms,

ascites, dyspnea, oliguria, and pleural effusion. In addition, the following symptoms have been

reported in association with this syndrome: pericardial effusion, anasarca, hydrothorax, acute

abdomen, hypotension, renal failure, pulmonary edema, intraperitoneal and ovarian hemorrhage,

deep venous thrombosis, torsion of the ovary, and acute respiratory distress. The early warning

signs of OHSS are abdominal pain and distention, nausea, vomiting, diarrhea, and weight gain.

Elevated urinary steroid levels, varying degrees of electrolyte imbalance, hypovolemia,

hemoconcentration, and hypoproteinemia may occur. Death due to hypovolemic shock,

hemoconcentration, or thromboembolism has occurred. Due to fragility of enlarged ovaries in

severe cases, abdominal and pelvic examination should be performed very cautiously. If

conception results, rapid progression to the severe form of the syndrome may occur.

To minimize the hazard associated with occasional abnormal ovarian enlargement

associated with CLOMID therapy, the lowest dose consistent with expected clinical results

should be used. Maximal enlargement of the ovary, whether physiologic or abnormal, may

not occur until several days after discontinuation of the recommended dose of CLOMID.

Some patients with polycystic ovary syndrome who are unusually sensitive to gonadotropin

may have an exaggerated response to usual doses of CLOMID. Therefore, patients with

polycystic ovary syndrome should be started on the lowest recommended dose and shortest

treatment duration for the first course of therapy (see DOSAGE AND

ADMINISTRATION).

If enlargement of the ovary occurs, additional CLOMID therapy should not be given until the

ovaries have returned to pretreatment size, and the dosage or duration of the next course should

be reduced. Ovarian enlargement and cyst formation associated with CLOMID therapy usually

regresses spontaneously within a few days or weeks after discontinuing treatment. The potential

benefit of subsequent CLOMID therapy in these cases should exceed the risk. Unless surgical

indication for laparotomy exists, such cystic enlargement should always be managed

conservatively.

A causal relationship between ovarian hyperstimulation and ovarian cancer has not been

determined. However, because a correlation between ovarian cancer and nulliparity, infertility,

and age has been suggested, if ovarian cysts do not regress spontaneously, a thorough evaluation

should be performed to rule out the presence of ovarian neoplasia.

Incidence of Adverse Events in Clinical Studies (Events Greater than 1%) (n =

8029*)

Incidence of Adverse Events in Clinical Studies (Events Greater than 1%) (n =

8029*)

Ovarian Enlargement

Vasomotor Flushes

Abdominal-Pelvic Discomfort/Distention/Bloating

Nausea and Vomiting

Breast Discomfort

Visual Symptoms

Blurred vision, lights, floaters, waves, unspecified visual complaints,

photophobia, diplopia, scotomata, phosphenes

Headache

Abnormal Uterine Bleeding

Intermenstrual spotting, menorrhagia

13.6

10.4

5.5

2.2

2.1

1.5

1.3

*Includes 498 patients whose reports may have been duplicated in the event totals and could not

be distinguished as such. Also, excludes 47 patients who did not report symptom data.

The following adverse events have been reported in fewer than 1% of patients in clinical trials:

Acute abdomen, appetite increase, constipation, dermatitis or rash, depression, diarrhea,

dizziness, fatigue, hair loss/dry hair, increased urinary frequency/volume, insomnia, lightheadedness,

nervous tension, vaginal dryness, vertigo, weight gain/loss.

Patients on prolonged CLOMID therapy may show elevated serum levels of desmosterol. This is

most likely due to a direct interference with cholesterol synthesis. However, the serum sterols in

patients receiving the recommended dose of CLOMID are not significantly altered. Ovarian

cancer has been infrequently reported in patients who have received fertility drugs. Infertility is a

primary risk factor for ovarian cancer; however, epidemiology data suggest that prolonged use of

clomiphene may increase the risk of a borderline or invasive ovarian tumor.

Postmarketing Adverse Events

The following adverse experiences were reported spontaneously with CLOMID. The cause and

effect relationship of the listed events to the administration of CLOMID is not known.

Dermatologic: Acne, allergic reaction, erythema, erythema multiforme, erythema nodosum,

hypertrichosis, pruritus

Central Nervous System: Migraine headache, paresthesia, seizure, stroke, syncope

Psychiatric: Anxiety, irritability, mood changes, psychosis

Visual Disorders: Abnormal accommodation, cataract, eye pain, macular edema, optic neuritis,

photopsia, posterior vitreous detachment, retinal hemorrhage, retinal thrombosis, retinal vascular

spasm, temporary loss of vision

Cardiovascular: Arrhythmia, chest pain, edema, hypertension, palpitation, phlebitis, pulmonary

embolism, shortness of breath, tachycardia, thrombophlebitis

Musculoskeletal: Arthralgia, back pain, myalgia

Hepatic: Transaminases increased, hepatitis

Neoplasms: Liver (hepatic hemangiosarcoma, liver cell adenoma, hepatocellular carcinoma);

breast (fibrocystic disease, breast carcinoma); endometrium (endometrial carcinoma); nervous

system (astrocytoma, pituitary tumor, prolactinoma, neurofibromatosis, glioblastoma multiforme,

brain abcess); ovary (luteoma of pregnancy, dermoid cyst of the ovary, ovarian carcinoma);

trophoblastic (hydatiform mole, choriocarcinoma); miscellaneous (melanoma, myeloma, perianal

cysts, renal cell carcinoma, Hodgkin’s lymphoma, tongue carcinoma, bladder carcinoma); and

neoplasms of offspring (neuroectodermal tumor, thyroid tumor, hepatoblastoma, lymphocytic

leukemia)

Genitourinary: Endometriosis, ovarian cyst (ovarian enlargement or cysts could, as such, be

complicated by adnexal torsion), ovarian hemorrhage, tubal pregnancy, uterine hemorrhage

Body as a Whole: Fever, tinnitus, weakness

Other: Leukocytosis, thyroid disorder

Fetal/Neonatal Anomalies. The following fetal abnormalities have also been reported during

postmarketing surveillance: delayed development; abnormal bone development including

skeletal malformations of the skull, face, nasal passages, jaw, hand, limb (ectromelia including

amelia, hemimelia, and phocomelia), foot, and joints; tissue malformations including imperforate

anus, tracheoesophageal fistula, diaphragmatic hernia, renal agenesis and dysgenesis, and

malformations of the eye and lens (cataract), ear, lung, heart (ventricular septal defect and

tetralogy of Fallot), and genitalia; as well as dwarfism, deafness, mental retardation,

chromosomal disorders, and neural tube defects (including anencephaly).