Jagsonpal
Pharmaceuticals
Pregnancy Disorders in India
However, several women in India do not get to live this dream and make these beautiful memories.
The moment a woman holds her new-born in her arms, she feels unimaginable joy - something every mother has a right to.
Female Infertility – Not so “Good News”
1 out of 3 infertile couples have been diagnosed with female infertility. Female infertility refers to a woman’s inability to conceive despite having regular and unprotected sexual intercourse for at least a year.
Reasons for infertility in women
One
Hormones & their effects on ovulation
Two
Age
Three
Damage to fallopian tubes
Four
Uterine causes
Five
Cervical condition
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Age – Late 30’s – difficult to conceive
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Polycystic Ovarian Syndrome (PCOS) - a common hormonal issue affecting several women of childbearing age
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Inability to Ovulate and Hormonal Issues - hormonal changes every month affecting egg release and conception
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Premature Ovarian Failure - a condition in which the ovaries don't release eggs or function normally
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Fallopian Tube Damage - damage to the woman's fallopian tubes, making it difficult for the sperm to reach the egg
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Endometriosis – a condition in which the uterine lining grows outside the uterus instead of inside – leading to infertility
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Unexplained reasons – Sexually transmitted diseases / Eating disorders / Alcohol or drug use / Fibroids / Thyroid problems / Stress
Recurrent Pregnancy Loss / Miscarriage - The “Sorrow” of Losing
15-25% of all pregnancies end in miscarriage - According to the WHO, 2.6 million babies are stillborn and an estimated 85 percent of miscarriages happen before the 12th week of pregnancy every year.
What can cause a miscarriage?
1
Poor Diet
2
Alcohol
3
Stress
4
Cigarettes
5
Drug Abuse
6
Obesity
7
Bacterial Infections
8
Excess Caffeine
9
Environmental Taxins
10
Hormonal Imbalance
11
Uterine Abnormalities
12
Chronic Medical Conditions
13
Mismatched Chromosomes
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Abnormality in the foetus - Pregnancy occurring out of the abnormal gametes will not be normal - it is Mother Nature’s way to discard and disallow these pregnancies from growing further
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Medical disorders in the mother - Uncontrolled diabetes, disorders of thyroid, obesity, high grade fever in early pregnancy can lead to a miscarriage
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Vitamin deficiency - Deficiency in folic acid is associated with a higher risk of early miscarriage
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Infections - Viral infections such as toxoplasmosis, rubella, herpes & bacterial infections, including urinary tract infections can cause miscarriages
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Deficiency of Hormones - Deficiency of hormones like progesterone can lead to early miscarriage
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Cervical incompetence - The mouth of the uterus i.e. cervix normally stays closed all throughout nine months and opens up at the time of delivery – If, the uterus opens up too early, it can lead to a miscarriage usually in the second trimester of pregnancy
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Uterine abnormalities – If uteri is in abnormal shape such as bicornuate uterus or develop a septum, these anomalies may lead to miscarriages
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Lifestyle - Habits such as smoking, drug use, malnutrition, excessive caffeine and exposure to radiation or toxic substances increasess chance of a miscarriage
Menstrual Disorders - The “Months” are not “NORMAL”
As per WHO, approximately 75% of females
experience problems associated with menstruation.
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4 out of 5 adolescent women suffer from painful periods
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2 out of 10 have irregular periods
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1 out of 10 have scanty bleeding
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1 out of 10 have prolonged bleeding
Types of menstrual disorders :
1
Abnormal Uterine Bleeding (AUB) include heavy menstrual bleeding, no menstrual bleeding (amenorrhea) or bleeding between periods (irregular menstrual bleeding)
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Heavy menstrual bleeding -
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1 out of 5 women bleed so heavily during their periods that they have to put their normal lives on hold just to deal with the heavy blood flow.
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Heavy menstrual bleeding can be common at various stages of woman’s life—during teen years when she first begins to menstruate and in late 40s or early 50s, as she gets closer to menopause.
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Heavy menstrual bleeding can be caused by hormonal imbalance, structural abnormalities in the uterus (such as poles or fibroids), other medical conditions (such as thyroid problems, blood clotting disorders, liver or kidney disease, leukemia, complications from IUD, miscarriage, and infections).
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No Menstrual Bleeding (amenorrhea) -
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When a female experiences no menstrual periods at all, the condition is called amenorrhea.
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In this condition, a female that has turned 16 but has not started menstruation, is likely linked to an issue in the endocrine system, which regulates hormones.
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Sometimes it is a result of low body weight to delayed maturing of the pituitary gland.
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When a female has had regular periods and then suddenly stops for three months or longer it can be caused by problems with estrogen levels.
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2
Painful Menstruation (dysmenorrhea)
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Most women have experienced menstrual cramps at some point during their lives. However, if cramps are exceptionally painful and persistent it is called dysmenorrhea.
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Pain from menstrual cramps is caused by uterine contractions.
3
Premenstrual Dysphoric Disorder (PMDD)
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An extreme PMS that significantly interferes with a woman’s life
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The most common symptoms of PMDD include heightened irritability, anxiety and mood swings.
4
Premenstrual Syndrome (PMS)
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4 out of 10 women experience symptoms of PMS - with over 100 possible symptoms of PMS
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The physical and psychological symptoms are associated with a female’s menstrual cycle include bloating, headaches, fatigue, painful breasts, anger, anxiety, mood swings, crying and depression
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Symptoms generally begin about a week before the period and disappear when the period begins or soon after.
Endometriosis - The “Growth” is not “NORMAL”
Endometriosis - a major reproductive disorder among over 25% women in India. Prevalence of endometriosis may be as high as 25% to 40% among infertile women & about 25 million women are estimated to be suffering from endometriosis in India.
Signs and symptoms:
1
Severe
Cramps
2
Heavy Periods
3
Pelvic Pain
4
Lower Back Pain
5
Pain
with Sex
6
Bloating / Nausea
7
Painful Urination
8
Infertility
9
Fatigue
10
Depression
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Endometriosis is a condition in which tissue that normally lines the inside of the uterus — also known as the endometrium — grows outside the uterus.
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The condition causes this endometrial tissue to grow in areas such as the ovaries, fallopian tubes or the tissue lining the pelvis, and can even spread beyond the pelvic region.
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The condition results in painful period and can lead to further complications.
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In the short term, it can result in pain within the individual, which is often more severe during their period. In the longer term, the build-up of cysts can impact the woman’s fertility.
Existing Treatment Options
Fertility restoration: Stimulating ovulation with fertility drugs
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Clomiphene citrate - stimulates ovulation by stimulating the growth of an ovarian follicle containing an egg
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Gonadotropins - These injected treatments stimulate the ovary directly to produce multiple eggs
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Metformin - Helps improve insulin resistance (in case of PCOS), which can improve the likelihood of ovulation
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Letrozole – Induce ovulation
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Bromocriptine - May be used when ovulation problems are caused by excess production of prolactin
Fertility restoration: Surgery
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Laparoscopic or hysteroscopic surgery - These surgeries can remove or correct abnormalities to help improve a woman’s chances of conceiving.
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Tubal surgeries - If fallopian tubes are blocked or filled with fluid (hydrosalpinx), the healthcare experts may recommend laparoscopic surgery to remove adhesions, dilate a tube or create a new tubal opening
Reproductive assistance
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Intrauterine insemination (IUI) - During IUI, millions of healthy sperm are placed inside the uterus close to the time of ovulation
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Assisted reproductive technology (ART) - IVF is the most effective assisted reproductive technology - involves retrieving mature eggs from a woman, fertilizing them with a man's sperm in lab, then transferring the embryos into the uterus after fertilization
The History of Fertility Treatment
Evolution and Promising Future
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1850’s - Artificial insemination - The biggest IVF breakthroughs - the first major development towards what would eventually come to be known as assisted reproductive technologies, or ART, including IVF. Dr. J. Martin Simms tried the procedure 55 times on six different women, but he did not take their ovulation cycles into account, and as a result, only one of the attempts resulted in pregnancy, which sadly ended in a miscarriage
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1880s - The first recorded case of artificial insemination by donor in 1884
Early steps towards IVF
1920s - 1940s - the hormones progesterone, oestrogen, and testosterone were all identified, and their roles in reproduction and pregnancy were closely studied.
1944 - Dr. John Rock of Harvard reported that the first US fertilisation of human eggs in a laboratory dish (in vitro) had occurred in his lab.
1980, the first American IVF clinic was opened, and a new age of fertility treatment had truly begun.
Dr. Buster with researchers Dr. Sydlee Cohen and
Dr. Maria Bustillo (Photo) in 1984 following the first successful human embryo transfer.
A timeline of modern day advanced treatments
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1980s - Egg donation
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The first successful egg donation pregnancies occurred in 1983, and since then there have been more than 50,000 live births from donor ova.
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1950s – 1990s - Frozen sperm, eggs, and embryos
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Cryopreservation, or the freezing of sperm, eggs and embryos, plays a huge role in IVF.
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Sperm was first frozen in 1953.
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The first successful pregnancy using previously frozen eggs was reported in 1984.
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The first live birth using a previously frozen embryo occurred in 1999.
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1980s - 1990s – ICSI
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Intracytoplasmic Sperm Injection (ICSI) was first performed in 1987, and the first successful birth resulting from ICSI occurred in 1992.
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1990s - PGS and PGD
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Preimplantation Genetic Screening (PGS) and Preimplantation Genetic Diagnosis (PGD) are used to ensure the genetic health of embryos before they are transferred.
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2010s - Time lapse photos/EmbryoScope
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One of the newest developments in fertility medicine is the EmbryoScope, a specialized incubator that takes time lapse photos of embryos as they develop. This cuts down the need to remove the embryos from the safety of the incubator multiple times during their development, limiting their exposure to any possible handling errors or airborne contaminants which could harm them.
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Advanced algorithms and artificial intelligence can be used to identify patterns in the way embryos develop, and has begun to suggest that the specific timings of cell divisions can be used to predict the potential viability of the embryo. All of this allows the very best and healthiest embryo for transfer, leading to much better outcomes for patients.
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Treatment Options for Menstrual Irregularities
Treatment for menstrual irregularities that are due to anovulatory bleeding (absent periods, infrequent periods, and irregular periods)
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Oral contraceptives
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Cyclic progestin
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Treatments for an underlying disorder that is causing the menstrual problem, such as counseling and nutritional therapy for an eating disorder
Treatment for menstrual irregularities that are due to ovulatory bleeding (heavy or prolonged menstrual bleeding) include
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Insertion of a hormone-releasing intrauterine device
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Use of various medications (such as those containing progestin or tranexamic acid) or nonsteroidal anti-inflammatory medications
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If the cause is structural or if medical management is ineffective, then the following may be considered:
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Surgical removal of polyps or uterine fibroids
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Uterine artery embolization, a procedure to block blood flow to the uterus
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Endometrial ablation, a procedure to cauterize (remove or close off by burning) blood vessels in the endometrial lining of the uterus
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Hysterectomy
Treatment for dysmenorrhea (painful periods) include
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Taking nonsteroidal anti-inflammatory medications
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Taking contraceptives, including injectable hormone therapy or birth control pills, using varied or less common treatment regimens
Introducing ProRetro
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Progesterone is the oldest known hormone.
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Natural progesterone and other molecules with pregestational activity are crucial in women’s health, particularly in reproductive medicine.
Regnier de Graaf - first description of the female reproductive system - Corpus luteum is recognized as the organ involved in pregnancy success.
1672
Louis-August Prenant and Gustav Born - Corpus luteum - an organ of internal secretion supporting the early embryo and facilitating implantation process in the uterus.
1898
Ernest Starling coined the term “hormone”.
1950
Second International Conference on the Standardization of Sex Hormones, London (England) - A compromise was made between the experts and the name progesterone (progestational steroidal ketone) was created.
1935
Butenandt and Ruzicka - awarded the Nobel Prize in Chemistry for researches on sex hormones.
1939
Russell Marker - obtained progesterone by natural precursors (the less expensive was extracted from the Dioscorea e mainly represented in Mexico).
1940
Georgeanna Seegar Jones - described for the first time luteal-phase deficiency as the cause of infertility; - She was credited with using progesterone to treat women with a history of miscarriages.
1949
Micronized progesterone - improved pharmacokynetic and pharmacodynamic profile; - for oral and vaginal use.
1980
“Modern progesterone era” - where we are now Progesterone and pro-gestational molecules are universally used in clinical practice.
Most important results in obstetrics derived from: 1) luteal-phase support in ART cycles; 2) recurrent pregnancy loss; 3) threatened miscarriage; 4) preterm birth prevention
Classification of Progestogens
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Compound with progesterone like action
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Progestogens can be Natural or Synthetic (Progestin)
Classification of Synthetic Progestins
Dydrogesterone – An Introduction
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Dydrogesterone contains progestin (female hormone) that plays a major role in regulating the menstrual cycles in females. It initiates the normal, regular growth as well as shedding of the womb lining. This helps induce regular periods in women who have menstrual irregularities due to lack of progesterone. Moreover, it relieves painful or absent periods, facilitates egg implantation and thus, treats infertility.
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It is a synthetic progestational hormone with no androgenic or estrogenic properties. Unlike many other progestational compounds, dydrogesterone produces no increase in temperature and does not inhibit ovulation.
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Only certain progestogens are to be used for pregnant women - Dydrogesterone is one of the progestogens, which are suitable to pregnancy. The following progestogens had been studied - Dydrogesterone (oral), Micronized progesterone (vaginal), 17- Hydroxyprogesterone caproate (intramuscular)
Dydrogesterone – Uses
Used to treat irregular duration of cycles and irregular occurrence and duration of periods caused by progesterone deficiency. Also used to prevent natural abortion in patients who have a history of habitual abortions.
Dydrogesterone – How it Works?
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Dydrogesterone is a progestogen that works by regulating the healthy growth and normal shedding of the womb lining by acting on progesterone receptors in the uterus.
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At therapeutic levels, dydrogesterone has no contraceptive effect as it does not inhibit or interfere with ovulation or the corpus luteum.
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Furthermore, dydrogesterone is non-androgenic, non-estrogenic, non-corticoid, non-anabolic and is not excreted as pregnanediol.
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This helps in the treatment of menstrual disorders such as absent, irregular or painful menstrual periods, infertility, premenstrual syndrome and endometriosis.
Therapeutic Indications & Dosage Regimen
Mode of administration
Mode of administration
Orally, May be taken with or without food
Indications | Route of Administration | Dosage Recommendation |
|---|---|---|
Menstrual Disorders | ||
Dysmenorrhea | Oral | 10 or 20 mg daily from day 5-25 of menstrual cycle. |
Dysfunctional Uterine Bleeding | Oral | Arrest of bleeding episode: 20 or 30 mg daily given for up to 10 days. Continuous treatment: 10 or 20 mg daily during the 2nd half of the menstrual cycle, initial treatment and duration will depend on cycle length. |
Secondary Amenorrhea | Oral | 10 or 20 mg daily for 14 days during the 2nd half of the assumed cycle. |
Premenstrual Syndrome | Oral | 10 mg bid starting on the 2nd half of the menstrual cycle until the 1st day of the next cycle, initial treatment and duration will depend on the cycle length. |
Irregular Menstrual Cycle | Oral | 10 or 20 mg daily starting on the 2nd half of menstrual cycle until 1st day of next cycle, initial treatment and duration will depend on the cycle length. |
Infertility | ||
Recurrent Miscarriage | Oral | 10 mg bid until the 12th week of pregnancy. |
Threatened Miscarriage | Oral | Initially, up to 40 mg followed by 20 or 30 mg daily until symptoms remit. |
Infertility due to Luteal Insufficiency | Oral | 10 or 20 mg daily starting on the 2nd half of menstrual cycle until the 1st day of the next cycle. Maintain treatment for at least 3 consecutive cycles. |
ART (Assisted Reproductive Technology) | ||
Luteal Phase Support (LPS in ART) | Oral | 30 mg daily from oocyte retrieval for 10 weeks until pregnancy is confirmed. |
For Luteal Phase support in Intrauterine insemination (IUI) | Oral | In IVF cycle From 3rd day –20 mg/d Dydrogesterone until the trigger day. |
For Luteal Phase support in progesterone-primed ovarian stimulation (PPOS) | Oral | In IVF cycle From 3rd day –20 mg/d Dydrogesterone until the trigger day. |
Other Disorders | ||
Endometriosis | Oral | 10-30 mg daily from day 5-25 of menstrual cycle or continuously for the entire cycle. |
Endometrial protection during menopausal hormonal replacement therapy | Oral | In addition to estrogen dose: Continuous sequential therapy: 10 mg daily for the last 14 days of every 28-day cycle. Cyclic therapy: 10 mg daily for the last 12-14 days of estrogen therapy; may be adjusted to 20 mg daily depending on the clinical response. |
Contraindications & Precautions
Contraindications
Do not take Proretro if you:
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are hypersensitive(allergic) to the active substance or to any of the excipients
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have a known or suspected progestogen dependent neoplasm
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have undiagnosed vaginal bleeding
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are using this medicine to prevent endometrial hyperplasia (abnormal growth of the lining of the uterus), specifically if you are also taking oestrogens
Special Precautions
Kindly talk to your doctor:
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If you have porphyria, herpes gestationis, otosclerosis, severe pruritus. history of depression, hepatic impairment
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If you are already Pregnant or Lactation
Patient Counselling
This drug may cause mild somnolence or dizziness, if affected, do not drive or operate machinery
Regular Monitoring
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Monitor liver function values
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Perform breast examination
Adverse Reactions
You many experience varying degrees (mild to moderate) of adverse effects (Kindly talk to your doctor)
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Bleeding and spotting, venous thromboembolism, menstrual disorders (e.g. metrorrhagia, menorrhagia, amenorrhoea, oligomenorrhoea, dysmenorrhoea and irregular menstruation), breast tenderness or pain, abnormal Liver Function Tests
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Gastrointestinal disorders: Nausea, vomiting.
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Increase in Weight
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Nervous system disorders: Migraine, headache, dizziness.
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Psychiatric disorders: Depressed mood.
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Skin and subcutaneous tissue disorders: Rash, pruritus, urticarial
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Potentially Fatal: Increased risk of breast cancer or rarely, ovarian cancer (when combined with oestrogen)
Jagsonpal proudly presents
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1st micronized Dydrogesterone in the world
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API of Dydrogesterone developed with Indigenous Research and Development in India
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Bioequivalent to innovator product
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Affordability at its best