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JAMA Jul 2021In the US, approximately 12.7% of reproductive age women seek treatment for infertility each year. This review summarizes current evidence regarding diagnosis and... (Review)
Review
IMPORTANCE
In the US, approximately 12.7% of reproductive age women seek treatment for infertility each year. This review summarizes current evidence regarding diagnosis and treatment of infertility.
OBSERVATIONS
Infertility is defined as the failure to achieve pregnancy after 12 months of regular unprotected sexual intercourse. Approximately 85% of infertile couples have an identifiable cause. The most common causes of infertility are ovulatory dysfunction, male factor infertility, and tubal disease. The remaining 15% of infertile couples have "unexplained infertility." Lifestyle and environmental factors, such as smoking and obesity, can adversely affect fertility. Ovulatory disorders account for approximately 25% of infertility diagnoses; 70% of women with anovulation have polycystic ovary syndrome. Infertility can also be a marker of an underlying chronic disease associated with infertility. Clomiphene citrate, aromatase inhibitors such as letrozole, and gonadotropins are used to induce ovulation or for ovarian stimulation during in vitro fertilization (IVF) cycles. Adverse effects of gonadotropins include multiple pregnancy (up to 36% of cycles, depending on specific therapy) and ovarian hyperstimulation syndrome (1%-5% of cycles), consisting of ascites, electrolyte imbalance, and hypercoagulability. For individuals presenting with anovulation, ovulation induction with timed intercourse is often the appropriate initial treatment choice. For couples with unexplained infertility, endometriosis, or mild male factor infertility, an initial 3 to 4 cycles of ovarian stimulation may be pursued; IVF should be considered if these approaches do not result in pregnancy. Because female fecundity declines with age, this factor should guide decision-making. Immediate IVF may be considered as a first-line treatment strategy in women older than 38 to 40 years. IVF is also indicated in cases of severe male factor infertility or untreated bilateral tubal factor.
CONCLUSIONS AND RELEVANCE
Approximately 1 in 8 women aged 15 to 49 years receive infertility services. Although success rates vary by age and diagnosis, accurate diagnosis and effective therapy along with shared decision-making can facilitate achievement of fertility goals in many couples treated for infertility.
Topics: Congenital Abnormalities; Female; Fertility Agents, Female; Humans; Infertility, Female; Infertility, Male; Life Style; Male; Ovulation Induction; Reproductive Techniques, Assisted; Semen Analysis
PubMed: 34228062
DOI: 10.1001/jama.2021.4788 -
Nature Reviews. Disease Primers Jan 2019Subfertility is common and affects one in six couples, half of whom lack an explanation for their delay in conceiving. Developments in the diagnosis and treatment of... (Review)
Review
Subfertility is common and affects one in six couples, half of whom lack an explanation for their delay in conceiving. Developments in the diagnosis and treatment of subfertility over the past 50 years have been truly remarkable. Indeed, current generations of couples with subfertility are more fortunate than previous generations, as they have many more opportunities to become parents. The timely access to effective treatment for subfertility is important as many couples have a narrow window of opportunity before the age-related effects of subfertility limit the likelihood of success. Assisted reproduction can overcome the barriers to fertility caused by tubal disease and low sperm count, but little progress has been made in reducing the effect of increasing age on ovarian function. The next 5-10 years will likely see further increases in birth rates in women with subfertility, a greater awareness of lifestyle factors and a possible refinement of current assisted reproduction techniques and the development of new ones. Such progress will bring challenging questions regarding the potential benefits and harms of treatments involving germ cell manipulation, artificial gametes, genetic screening of embryos and gene editing of embryos. We hope to see a major increase in fertility awareness, access to safe and cost-effective fertility care in low-income countries and a reduction in the current disparity of access to fertility care.
Topics: Adult; Age Factors; Female; Fertility Agents; Humans; Hysterosalpingography; Infertility, Female; Mass Screening; Middle Aged; Risk Reduction Behavior
PubMed: 30679436
DOI: 10.1038/s41572-018-0058-8 -
Fertility and Sterility Dec 2016Primary ovarian insufficiency (POI) is a rare but important cause of ovarian hormone deficiency and infertility in women. In addition to causing infertility, POI is... (Review)
Review
Primary ovarian insufficiency (POI) is a rare but important cause of ovarian hormone deficiency and infertility in women. In addition to causing infertility, POI is associated with multiple health risks, including bothersome menopausal symptoms, decreased bone density and increased risk of fractures, early progression of cardiovascular disease, psychologic impact that may include depression, anxiety, and decreased perceived psychosocial support, potential early decline in cognition, and dry eye syndrome. Appropriate hormone replacement therapy (HRT) to replace premenopausal levels of ovarian sex steroids is paramount to increasing quality of life for women with POI and ameliorating associated health risks. In this review, we discuss POI and complications associated with this disorder, as well as safe and effective HRT options. To decrease morbidity associated with POI, we recommend using HRT formulations that most closely mimic normal ovarian hormone production and continuing HRT until the normal age of natural menopause, ∼50 years. We address special populations of women with POI, including women with Turner syndrome, women with increased risk of breast or ovarian cancer, women approaching the age of natural menopause, and breastfeeding women.
Topics: Adult; Estrogen Replacement Therapy; Female; Fertility Agents, Female; Humans; Infertility, Female; Menopause, Premature; Middle Aged; Patient Selection; Primary Ovarian Insufficiency; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 27912889
DOI: 10.1016/j.fertnstert.2016.09.046 -
Acta Obstetricia Et Gynecologica... Oct 2018The objective of this narrative review was to suggest a rational order of treatment choices in anovulatory women with polycystic ovary syndrome (PCOS), for whom a... (Review)
Review
The objective of this narrative review was to suggest a rational order of treatment choices in anovulatory women with polycystic ovary syndrome (PCOS), for whom a multitude of treatment options exist. In obese/overweight women with PCOS the importance of weight reduction should be stressed. Inositol, a dietary supplement with a documented effect on ovulation and without adverse effects in the doses recommended, may be suggested. Additional first-line medical alternatives include insulin sensitizers, selective estrogen receptor modulators, and aromatase inhibitors. Of these, the aromatase inhibitor letrozole and the combination of clomiphene citrate and metformin have the highest rates of ovulation and live birth. Second-line treatments are ovarian electrocautery and low-dose follicle-stimulating hormone stimulation. Controlled ovarian stimulation with in vitro fertilization, should be considered the last option as it carries a significant risk of ovarian hyperstimulation syndrome in patients with PCOS.
Topics: Female; Fertility Agents, Female; Humans; Infertility, Female; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 29889977
DOI: 10.1111/aogs.13395 -
Biomedicine & Pharmacotherapy =... Dec 2021Melatonin, mostly released by the pineal gland, is a circadian rhythm-regulated and multifunctional hormone. Great advances in melatonin research have been made,... (Review)
Review
Melatonin, mostly released by the pineal gland, is a circadian rhythm-regulated and multifunctional hormone. Great advances in melatonin research have been made, including its role in rhythms of the sleep-wake cycle, retardation of ageing processes, as well as antioxidant or anti-inflammatory functions. Melatonin can scavenge free radicals such as reactive oxygen species (ROS), a key factor in reproductive functions. Melatonin plays an important role in oocyte maturation, fertilization and embryonic development as well. The concurrent use of melatonin increases the number of mature oocytes, the fertilization rate, and number of high-quality embryos, which improves the clinical outcome of assisted reproductive technology (ART). This review discusses the relationship between melatonin and human reproductive function, and potential clinical applications of melatonin in the field of reproductive medicine.
Topics: Animals; Embryo Transfer; Embryonic Development; Female; Fertility; Fertility Agents; Fertilization in Vitro; Free Radical Scavengers; Humans; In Vitro Oocyte Maturation Techniques; Infertility; Male; Melatonin; Ovary; Oxidative Stress; Reactive Oxygen Species; Reproduction; Reproductive Medicine; Reproductive Techniques, Assisted
PubMed: 34624677
DOI: 10.1016/j.biopha.2021.112001 -
The New England Journal of Medicine Jul 2014Clomiphene is the current first-line infertility treatment in women with the polycystic ovary syndrome, but aromatase inhibitors, including letrozole, might result in... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Clomiphene is the current first-line infertility treatment in women with the polycystic ovary syndrome, but aromatase inhibitors, including letrozole, might result in better pregnancy outcomes.
METHODS
In this double-blind, multicenter trial, we randomly assigned 750 women, in a 1:1 ratio, to receive letrozole or clomiphene for up to five treatment cycles, with visits to determine ovulation and pregnancy, followed by tracking of pregnancies. The polycystic ovary syndrome was defined according to modified Rotterdam criteria (anovulation with either hyperandrogenism or polycystic ovaries). Participants were 18 to 40 years of age, had at least one patent fallopian tube and a normal uterine cavity, and had a male partner with a sperm concentration of at least 14 million per milliliter; the women and their partners agreed to have regular intercourse with the intent of conception during the study. The primary outcome was live birth during the treatment period.
RESULTS
Women who received letrozole had more cumulative live births than those who received clomiphene (103 of 374 [27.5%] vs. 72 of 376 [19.1%], P=0.007; rate ratio for live birth, 1.44; 95% confidence interval, 1.10 to 1.87) without significant differences in overall congenital anomalies, though there were four major congenital anomalies in the letrozole group versus one in the clomiphene group (P=0.65). The cumulative ovulation rate was higher with letrozole than with clomiphene (834 of 1352 treatment cycles [61.7%] vs. 688 of 1425 treatment cycles [48.3%], P<0.001). There were no significant between-group differences in pregnancy loss (49 of 154 pregnancies in the letrozole group [31.8%] and 30 of 103 pregnancies in the clomiphene group [29.1%]) or twin pregnancy (3.4% and 7.4%, respectively). Clomiphene was associated with a higher incidence of hot flushes, and letrozole was associated with higher incidences of fatigue and dizziness. Rates of other adverse events were similar in the two treatment groups.
CONCLUSIONS
As compared with clomiphene, letrozole was associated with higher live-birth and ovulation rates among infertile women with the polycystic ovary syndrome. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT00719186.).
Topics: Adult; Clomiphene; Double-Blind Method; Female; Fertility Agents, Female; Humans; Infertility, Female; Kaplan-Meier Estimate; Letrozole; Live Birth; Luteal Phase; Male; Nitriles; Ovulation; Polycystic Ovary Syndrome; Pregnancy; Quality of Life; Triazoles
PubMed: 25006718
DOI: 10.1056/NEJMoa1313517 -
Journal of the Chinese Medical... Nov 2018
Topics: Fertility; Fertility Agents
PubMed: 30201190
DOI: 10.1016/j.jcma.2018.07.003 -
Fertility and Sterility Jun 2016
Topics: Adult; Female; Fertility Agents, Female; Humans; Infertility, Female; Maternal Age; Ovarian Reserve; Ovary; Ovulation; Ovulation Induction; Patient Selection; Pregnancy; Risk Assessment; Risk Factors; Treatment Failure
PubMed: 26921622
DOI: 10.1016/j.fertnstert.2016.02.005 -
Fertility and Sterility Sep 2021To determine whether vaginal progesterone for programmed endometrial preparation is noninferior to intramuscular progesterone in terms of live birth rates from frozen... (Comparative Study)
Comparative Study
OBJECTIVE
To determine whether vaginal progesterone for programmed endometrial preparation is noninferior to intramuscular progesterone in terms of live birth rates from frozen embryo transfer (FET).
DESIGN
Three-armed, randomized, controlled noninferiority trial.
SETTING
Multicenter fertility clinic.
PATIENT(S)
A total of 1,346 volunteer subjects planning vitrified-warmed transfer of high-quality nonbiopsied blastocysts were screened, of whom 1,125 subjects were ultimately enrolled and randomly assigned to treatment.
INTERVENTION(S)
The subjects were randomly assigned to receive, in preparation for FET, 50 mg daily of intramuscular progesterone (control group), 200 mg twice daily of vaginal micronized progesterone plus 50 mg of intramuscular progesterone every third day (combination treatment), or 200 mg twice daily of vaginal micronized progesterone.
MAIN OUTCOME MEASURE(S)
The primary outcome was live birth rate per vitrified-warmed embryo transfer. The secondary outcomes were a positive serum human chorionic gonadotropin test 2 weeks after FET, biochemical pregnancy loss, clinical pregnancy, clinical pregnancy loss, total pregnancy loss, serum luteal progesterone concentration 2 weeks after FET, and patient's experience and attitudes regarding the route of progesterone administration, on the basis of a survey administered to the subjects between FET and pregnancy test.
RESULT(S)
A total of 1,060 FETs were completed. The live birth rate was significantly lower in women receiving only vaginal progesterone (27%) than in women receiving intramuscular progesterone (44%) or combination treatment (46%). Fifty percent of pregnancies in women receiving only vaginal progesterone ended in miscarriage.
CONCLUSION(S)
The live birth rate after vaginal-only progesterone replacement was significantly reduced, due primarily to an increased rate of miscarriage. Vaginal progesterone supplemented with intramuscular progesterone every third day was noninferior to daily intramuscular progesterone, offering an effective alternative regimen with fewer injections.
CLINICAL TRIAL REGISTRATION NUMBER
NCT02254577.
Topics: Abortion, Spontaneous; Administration, Intravaginal; Adult; Cryopreservation; Drug Administration Schedule; Embryo Transfer; Female; Fertility; Fertility Agents, Female; Fertilization in Vitro; Humans; Infertility; Injections, Intramuscular; Live Birth; Pregnancy; Pregnancy Rate; Progesterone; Time Factors; Treatment Outcome; United States
PubMed: 33992421
DOI: 10.1016/j.fertnstert.2021.04.013 -
Asian Journal of Andrology 2016Many controversial topics regarding Andrology in general, and male infertility more specifically have been discussed and debated for decades. Numerous manuscripts and...
Many controversial topics regarding Andrology in general, and male infertility more specifically have been discussed and debated for decades. Numerous manuscripts and entire journals have been dedicated to the dissemination of standardized information with multiple reviews covering similar topics. This massive amount of data leads to difficulty identifying pertinent clinical practice guidelines. Furthermore, detailed instructions on how to manage common clinical conditions tend to be diluted by copious amounts of text and superfluous information.
Topics: Androgens; Andrology; Chronic Pain; Fertility; Fertility Agents, Male; Humans; Infertility, Male; Male; Testicular Diseases; Testosterone; Varicocele; Vasovasostomy
PubMed: 27048783
DOI: 10.4103/1008-682X.179141