​Kembara Xtra - Medicine - Infertility

​Kembara Xtra - Medicine - Infertility 
Definition: Failure to become pregnant after one year of regular sexual activity without the use of contraception in women under 35, or failure to become pregnant after six months of regular activity without the use of contraception in women over 35. Primary infertility: Never-pregnant couple.
Secondary infertility: Couple has been pregnant.

 Incidence
The probability of becoming pregnant within a year is known as incidence. Age-related increases in the prevalence of infertility are accompanied by fertility declines that begin in the early 30s and accelerate in the late 30s. 85% of couples will become pregnant within a year of unprotected sexual activity. Within 24 months of unprotected sexual activity, 95% of couples will become pregnant.


Prevalence
Infertility affects about 25% of couples at some point in their reproductive lives; according to the National Survey of Family Growth, 9% of couples between the ages of 15 and 34, 25% of couples between the ages of 35 and 39, and 30% of couples between the ages of 40 and 44 meet the criteria for being infertile.


Pathophysiology and Etiology 
The majority of instances are multifactorial, with about 35% of cases being caused by female factors (of which 21% are caused by ovulatory dysfunction and 14% by tubal injury); 26% being caused by male causes; and 28% being of undetermined etiology.
• Obtained: Pelvic inflammatory disease (PID), endometriosis, polycystic ovary syndrome (PCOS), premature ovarian failure, and advanced maternal age are the most frequent causes of infertility in the United States.
Low fertility caused by insufficient egg production or poor oocyte quality is known as diminished ovarian reserve (DOR). Anatomical and genetic abnormalities are known as congenital.


Genetics The infertile population has a higher frequency of genetic disorders such Klinefelter syndrome (47,XXY), Turner syndrome (45X or mosaic), and fragile X syndrome.

Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation producing congenital bilateral absence of vas deferens (CBAVD) is identified in 16% of males with azoospermia/severe oligozoospermia. Y chromosomal microdeletions are related with localized abnormalities of spermatogenesis.

Female-specific risk factors include advanced age, endocrinopathy, autoimmune disease, undetected celiac disease, collagen vascular disorders, thrombophilia, obesity, cancer, and gynecologic history including irregular/abnormal menses, STIs, dysmenorrhea, and fibroids.
Appendicitis, pelvic surgery, intrauterine surgery, and tubal ligation in the past surgically; smoking, alcohol/substance abuse, eating disorders, exercise, and advanced maternal age in the past socially;
Male - Medical history includes cancer, endocrinopathy, STIs, prostatitis, and drug use (including -blockers, calcium channel blockers, and antiulcer medications).
- Surgical past: vasectomy with or without reversal, orchiopexy, hernia repair
- Social: smoking, binge drinking, using anabolic steroids, being exposed to the environment, working in tight clothing or saunas frequently, and taking prescription medications that reduce male virility.

Prevention 
Regular diet and exercise, abstain from smoking and other drug usage, and prevent STIs

Accompanying Conditions 

(Hyperandrogenism, PCOS) Pelvic pathology, endocrine dysfunction, and anovulation

Presenting History: Full female reproductive history, including age at menarche, menstrual cycle regularity, physical development (Tanner phases), prior methods of contraception, and history of aberrant Pap smears and medical care
Coital frequency and timing; history of sexual dysfunction; history of STIs; history of endocrine abnormalities; history of malignancy or chronic illness; history of vasectomy; history of pelvic/abdominal surgery; history of abortion; dilation and curettages; bilateral tubal ligations; vasectomy; or any other abdominal/pelvic surgery; medications; drug abuse; allergies; and exposure to environmental dangers.

Clinical Assessment 
Female - Pubertal development with Tanner staging - indicators of PCOS: androgen excess, obesity, indicators of insulin resistance Body mass index (BMI), distribution of body fat, and waist circumference
Examine the rugation, discharge, and anatomical diversity in the vagina.
Male - Abnormalities of the penis or urethral meatus - Abnormalities of the uterine size/shape, mobility, and tenderness - Testes: volume, symmetry, masses (varicocele, hydrocele), and the presence or absence of the vas deferens


Laboratory Results 

Initial examinations (lab, imaging)
History guides evaluation:
Inconsistent or irregular menstruation as an indicator of ovulation
– Ovarian insufficiency is indicated by high levels of the follicle-stimulating hormone (FSH) and luteinizing hormone (LH), but low levels of estradiol. LH levels alone can indicate PCOS.
Although basal body temperature (BBT) charts are not an accurate approach for predicting ovulation, they are inexpensive and may be helpful for some couples to plan the timing of their intimate relations.

Women older than 35 years old should have their ovarian reserve evaluated. An FSH >15 to 20 IU/L on day 3 of menstruation is symptomatic of inadequate reserve.
- Antral follicle counts (AFCs) are the number of antral follicles determined by transvaginal ultrasonography (US).As a woman gets closer to menopause, her AMH drops.AMH is measurable at any point in the cycle and is unaffected by hormones.. - Clomiphene challenge test: Measure FSH of 10 mIU/mL on day 10 after taking clomiphene from days 5 to 9 to confirm the diagnosis of DOR.Semen analysis is recommended for all infertile couples.Male reproductive potential is not solely determined by the analysis of the sperm.Semen is collected after two to five days of abstinence.Due to the inherent diversity within a single individual, repeat the test 2 to 3 times.Semen volume must be 1.5 mL or greater, pH must be 7.2 or greater, sperm concentration must be 15 million spermatozoa per mL or greater, total sperm count must be 39 million spermatozoa per ejaculate or greater, total motility must be 40% or greater, or 32% or greater with progressive motility, vitality must be 58% or greater live spermatozoa, and sperm morphology (percentage of normal forms) muste Additional laboratory17-hydroxyprogesterone, prolactin, thyroid-stimulating hormone, androgen levels, as well as fast plasma reagin, hepatitis B, chlamydia, gonorrhea, and CMV: Family history-based genetic testingHysterosalpingogram (HSG), which can be used for both diagnostic and therapeutic purposes, to assess the patency of the tubes and the shape of the cavity. Transvaginal ultrasound for anatomic anomalyc

Tests in the Future & Special Considerations
Imaging abnormalities might need to be evaluated surgically.
Other/Diagnostic Procedures

Laparoscopy: utilized to directly observe the peritoneal cavity and may be indicated to evaluate abnormal findings on HSG. Hysteroscopy: the gold standard for directly observing the endometrial cavity; may be indicated to evaluate filling defects on HSG or SHG. Endometriosis can only be accurately diagnosed through laparoscopy.


Management 
Achieving a healthy BMI, quitting smoking, reducing caffeine and alcohol consumption, and delaying the infertility evaluation for at least a year are all lifestyle modifications that may increase fertility.
Couples may want to start with less complicated ovulation detection techniques. For certain people, BBT monitoring and/or LH surge detection may be useful. BBT is not as accurate in predicting ovulation as other techniques.
● Be aware of each patient's insurance coverage. Keep an eye on how the pair is feeling emotionally: A lot of people experience depression, rage, anxiety, and marital strife. Measures of support and counseling are beneficial to many patients.
All female patients seeking in vitro fertilization should receive a daily oral folate supplementation of 1 mg. Males' dietary carotenoids may enhance the quality of their sperm.
● The best fertility treatment for women with unexplained infertility who haven't gotten pregnant after two years of regular, unprotected sex is in vitro fertilization (IVF):
– The female's eggs are taken out and fertilized externally. On days 3 or 5, the embryo is placed into the uterus after being watched for 3 to 5 days.
An early referral for IVF should be made for anatomic issues, albeit a surgical evaluation may be necessary.
- Patients receiving IVF for anatomical causes rather than ovulatory malfunction have experienced fewer side effects (poor APGAR scores, diabetes mellitus).
- Subfertile women who gave birth naturally without IVF have also been found to have an elevated risk of preterm birth and low birth weight compared to the general population.
– One can get donor eggs.
- Women under the age of 40 or those who have had 12 cycles of artificial insemination or two years of unprotected sex should be given the option of three full cycles of IVF.
– Women between the ages of 40 and 42 who have minimal ovarian reserves or no history of IVF should be given the option of one complete cycle.
The use of intrauterine insemination (IUI) without ovarian stimulation may be appropriate in certain situations, such as those involving people in same-sex partnerships or those with physical limitations that prevent vaginal sex.

Male factors: Take into account a change in lifestyle.
- IUI: The uterus is directly injected with sperm via a catheter.
The sperm count is effectively increased by IUI.
- For males with significant abnormalities (i.e., 5 million sperm) or those who were unable to conceive with IUI, intracytoplasmic sperm injection (ICSI) is carried out in conjunction with IVF. Direct injection of one sperm into the cytoplasm of the egg. 70% of the time, fertilization takes place.
– Sperm from donors can be obtained.

First Line of Medicine

The etiology of infertility affects the course of treatment.
Achieving an ideal BMI of between 17 and 29 kg/m2 Women:
- To assess whether an anovulatory woman is HYPOgonadotropic or NORMOgonadotropic-
 
Patients who are hypogonadotropic: Daily injections of both FSH and LH are the standard method for inducing ovulation. These injections must be closely managed to prevent overstimulation, which can cause ovarian hyperstimulation syndrome (OHSS).
Patients who are normogonadotropic typically have PCOS. Letrozole, an aromatase inhibitor, may be more effective than clomiphene for PCOS individuals seeking to induce ovulation. Clomiphene citrate (Clomid) Unexplained infertility: Controlled ovarian hyperstimulation, such as with clomiphene citrate and IUI, may be used as the first-line treatment. IVF could be suggested as a backup plan.
- Cervical or genital issues: IUI
- IVF or surgery for endometriosis; medication therapy does not boost pregnancy rates.
- A shift in lifestyle that includes more frequent and earlier sex
● Male:
- A shift in lifestyle that includes more frequent and earlier sex
- Modifications to some selective serotonin reuptake inhibitor, calcium channel blocker, and highly active antiretroviral therapy drugs to increase sperm count, testicular function, sperm production, and quality.
- Surgery: removing sperm blockages (such as varicocele or a vasectomy); - Sperm retrieval when ejaculation is difficult.
Next Line
Metformin is helpful in anovulatory PCOS women, especially those who have glucose intolerance; start with 500 mg daily and progress to 1,500 mg/day while monitoring renal function; it may take up to 3 months before it becomes effective.
Consider using oral contraceptives (OCPs) for two cycles before stopping them and starting the clomiphene again right away.
When prolactin levels are high or there is no withdrawal bleeding following progesterone therapy, cabergoline or bromocriptine are utilized. The medicine can be stopped once conception has happened.
Recombinant FSH or human menopausal gonadotropins (hMGs) should be used if there is clomiphene resistance or hypogonadotropism.

Urology and/or reproductive endocrinology referral

Additionally Treatment 
If a woman is unable to become pregnant, think about using surrogacy.

Surgical Techniques 

For people whose infertility has anatomical origins, reproductive surgery can be required. For hydrosalpinx, polypectomy, myomectomy, and salpingectomy are all used. Think about sperm aspiration and varicocele therapy.

Alternative Therapies 
With IVF, acupuncture may boost the live birth rate.

If oral ovulation induction is unsuccessful after three to six cycles, consult a follow-up specialist.
patient observation
Monitoring the cycle could reduce dangers. The amount of developing follicles every cycle can be displayed using US.
Low-caffeine diet, moderate alcohol consumption



Prognosis 
The majority of couples (80%–90%) will become pregnant within 12 months after trying to become pregnant through routine unprotected sexual contact. Fecundability  gradually declines with time.


Complications 

Women with infertility diagnoses and those undergoing fertility therapy are at a higher risk of maternal morbidity than women who are fertile. These factors include anxiety, multiple pregnancies, OHSS, and a minor increase in the likelihood of congenital abnormalities.