Fertility Issues

Preimplantation genetic testing (PGT) is the general term for genetic testing performed on embryos produced by in vitro fertilization (IVF) before the embryos are transferred to the uterus. The purpose of PGT is to improve the chances of having a successful embryo transfer.

Genetic testing does not impact or change the genetics of an embryo, but it does give doctors and prospective parents more information and may help them select the most viable embryos for transfer.  

There are three types of PGT: PGT for monogenic disorders (PGT-M), PGT for structural chromosomal rearrangements (PGT-SR), and PGT for aneuploidy (PGT-A). PGT-A is the most routine type performed and as such should be understood by prospective parents.

In recent years, red light therapy, also known as phototherapy or light-emitting diode (LED) light therapy, has gained attention as a potential tool to enhance fertility in both men and women. This article will explore red light therapy and its impact on reproductive health. This includes who can benefit from it, the safety of red light therapy, and how it may potentially improve factors such as blood flow and cellular energy.

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Red light, which has a wavelength between 620-750 nanometers (nm), contains energy that may become absorbed by target cells. Infrared light (750-1000nm) is also sometimes used in low light therapy, and even called red light therapy, despite it being in the infrared range. In comparison to other visible wavelengths, red light is better able to penetrate deeper tissues due to a longer wavelength.ⁱ Light with longer wavelengths has lower energy compared to light with shorter wavelengths. Red light therapy utilizes a type of light emitting diode (LED) light which emits a relatively low level of energy in comparison to non-visible light or UV lights.ⁱⁱ  

Red light therapy is often referred to as low level light therapy (LLLT), low-level laser irradiation, or laser acupuncture. In addition, it is believed that exposure to red light is not associated with DNA damage, unlike UV light which is known to increase the occurrence of skin cancer.ⁱⁱⁱ  

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There are a variety of proposed mechanisms as to how exactly red light therapy works, and the exact mechanism remains unclear.^iv  Exposure of human cells to certain light intensities has been shown to increase cellular processes, including cell proliferation (increase in cell number) and metabolism.^v,viIt has been proposed that the energy emitted by red light triggers these beneficial cellular responses when the energy is absorbed by mitochondria,^vii which are present in varying quantities in almost all cells. Mitochondria are cellular structures that produce energy in the form of adenosine triphosphate (ATP), which is utilized by the cell.^viii,ix

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Red and near infrared light have been used clinically as a noninvasive therapy for many years in fields other than fertility, including dermatology, dentistry, and neurology. For example, it has been used to promote wound healing and treat chronic joint pain.^x,xi It is believed that the benefits connected to red light therapy are based on improvements in blood flow and angiogenesis (creation of new blood vessels).^{xii, xiii} This is believed to occur due to changes in a chemical compound called nitric oxide (NO), which is discussed below.^xiv

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Can red light therapy improve fertility outcomes?

As discussed, red light therapy has been shown to have certain clinical benefits in other fields, and research into red light therapy for fertility may one day support its clinical application. Photobiomodulation via red light therapy is believed to enhance mitochondrial energy production, particularly in stressed cells.^xv This is relevant to eggs and sperm because they both require a high quantity of mitochondria for their functional needs. For example, the oocyte contains an extremely large number of mitochondria (100,000-100,000,000) compared to other types of cells,^xvi which is necessary due to the large energy demands of oogenesis and later in embryonic development.^{xvii, xviii}  The sperm cell midpiece contains approximately 50-75 mitochondria, which is a high density for the small cellular area it occupies.^xix  

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Mitochondria from sperm do not become incorporated into the resulting embryo, although they are critical for sperm fertilizing capabilities. Embryonic mitochondria are derived from the oocyte and play a large role in energy production during early embryonic development.^xx,xxi Thus, red light therapy may have potential applications in fertility for mitochondrial energy production, as eggs and sperm rely on mitochondria for their energy needs during the reproductive process.

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Further, red light therapy has also been shown to increase blood flow to treated tissues, which is believed to be mediated by an increase in nitric oxide (NO) formation.^xxii,xxiii Nitric oxide, an effective antioxidant, acts to maintain healthy physiological levels of reactive oxygen species (ROS). The body requires a certain level of ROS for proper cellular function; however, increased ROS levels cause a state of oxidative stress. Aging is associated with an increase in ROS accompanied by a decrease in antioxidants which counteract negative ROS effects. Oxidative stress has well-documented detrimental impacts on both male and female fertility.^xxiv,xxv Hence, in theory, red light therapy may address age-related fertility concerns by improving blood flow and reducing oxidative stress.

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Overall, proper oocyte and sperm cell mitochondrial function is imperative for fertility. Given the proposed advantages of red light therapy on the mitochondrial function in other cell types,^{xxvi, xxvii} there is the potential for improvement in fertility with the use of red light therapy. Furthermore, its capacity to reduce oxidative stress, a common issue in age-related fertility concerns, adds another dimension to its potential benefits in this context. While this means that fertility benefits remain plausible via these mechanisms, evidence supporting its use and mechanism of action are still lacking (discussed below).

Red light therapy for male infertility: research evidence

Sperm cells rely heavily upon mitochondrial ATP production for optimal sperm motility and physiological reactions necessary for fertilization.^xxviii Some research findings suggest there may be beneficial effects of LED red light on sperm cells.^{xxix, xxx, xxxi} The potential benefits may include increased cell survival and motility.  

One of the first studies to investigate laser light exposure, conducted in the early 1980s, suggested human ejaculate exposure to red laser light could stimulate motility in live sperm cells that were previously non-motile; however, no differences in sperm velocity were noted and the effects on reproductive outcomes (i.e. clinical pregnancy or live birth rates) were not investigated in the study.^xxxii  

A different small study found that red light exposure of frozen-thawed human sperm samples resulted in a significantly increased velocity compared to non-treated sperm. ^xxxiii While the study observed no significant level of DNA damage induced by red light therapy, there was again no impact of red light therapy on reproductive outcomes.^xxxiv

In 2014, researchers from Iran published findings examining the effects of red light therapy on human sperm motility using fresh semen specimens from patients with low sperm motility (called asthenospermia).^xxxv The findings showed that sperm cells exposed to a low level laser had increased progressive motility^xxxvi It should be noted that the wavelength of light used in this study was in the infrared range, just outside of the red light range, as described above.

These three studies examining the effects of low light therapy were performed on sperm cells collected from human ejaculate. However, the potential effects of direct exposure of the testes to red light in humans are not well-documented. Data collected from animal studies suggest photobiomodulation therapy impacts sperm quality when applied directly to the testes. Mice with heat-induced azoospermia, or lack of sperm, due to elevated testicular temperatures, underwent testicular IR laser exposure over the course of 21 days.^xxxvii Researchers found the mice receiving testicular laser treatment experienced a restoration of sperm cell production and overall healthier testicular tissue in comparison to the non-laser-exposed mice.^xxxviii  

One very small clinical study in Indonesia examined the effect of direct testicular irradiation in humans.  The 20 study participants had each testicle irradiated for four minutes two times per week. for a total of 10 sessions.^xxxix Laser treatment in men with azoospermia (absence of sperm in the ejaculate) did not lead to an improvement in sperm count. However, men with oligospermia (low sperm count) had an average 2.7-fold and 3.6-fold increase in sperm counts.^xl No adverse effects were reported by any of the 20 men included in the study.^xli There is a lack of good quality and validated published evidence related to using red light therapy directly on the testes, and further studies are needed.^xlii

Overall, there is little published evidence supporting the use of red light therapy for male fertility in humans. Furthermore, in the published studies showing potential improvement to sperm, the impact on reproductive outcomes, such as live birth rates, has not been studied.  

Red light therapy for female infertility: research evidence

It is well documented that fertility decreases with age in women, especially as they approach their mid 30s.^xliii,xliv One major factor driving this decline in female fertility associated with age is decreased oocyte quality.^xlv The occurrence of aneuploidy (having too few or too many copies of a chromosome), becomes more common as women get older, likely due to the impact of age on chromosomes.  

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In addition, aging oocytes contain aged mitochondria which may not be as efficient at energy production.^{xlvi,xlvii,xlviii,xlix} Mitochondria are the energy organelles inside of cells. Oocytes contain a very high number of mitochondria which provide large amounts of energy to the oocyte during maturation and throughout early embryonic development.^{l,li,lii,liii} Therefore, as red light therapy is believed to improve cellular mitochondrial function, there is the potential for red light therapy to also improve mitochondrial metabolism in aging oocytes. However, more research is needed to verify this experimentally and clinically.  

There are very few research studies that have thoroughly characterized the effect of red light therapy on female fertility. In 2010, a Japanese research group reported a clinical study where the effect of an IR laser (830 nm) was examined in female patients seeking fertility treatment.^liv Although they observed that the women who became pregnant had received more IR therapy sessions than those that did not become pregnant (3.1 vs 2.6 sessions),^lv there are various limitations to the study that prevent the results from being generalizable. For example, most of the patients were over 40 years old, with over half >43yr in the non-pregnant group, and the pregnancy rate was very low (16.5 percent, 97/491).^lvi Additionally, details of the specific type(s) of infertility treatment patients received was not described. We included the study here to demonstrate the paucity of quality research in this area. Because of the study limitations, conclusions on any fertility impact cannot be made from these results.

Another study, from Iran, assessed the ability of direct red light exposure to help improve the maturation of immature oocytes retrieved from 36 women with polycystic ovarian syndrome (PCOS) following ovarian stimulation for IVF.^lvii The oocytes exposed to red light (640nm) had a significantly higher rate of in vitro maturation (IVM, 111/155 reached MII mature stage) compared to the non-exposed control oocytes (78/159 reached MII stage).^lviii This was also accompanied by a decline in reactive oxygen species (ROS) compared to controls. The impact on fertilization rates or IVF outcomes were not investigated in the study.^lix

Animal models have also been utilized to study the effects of photobiomodulation on female fertility. Using a rat model of PCOS, treatment with red light therapy was found to decrease the number of ovarian cysts while increasing ovulation and follicle number, compared to a PCOS control group.^lx The findings have not yet been validated in humans.

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Another frequent cause of female infertility, poor endometrial receptivity, is a result of endometrial conditions inconducive to embryo implantation. One factor that may contribute to poor implantation is inadequate endometrial thickness.^lxi As red light laser therapy is known to enhance cell proliferation (cell division), it is being examined as a therapy method to increase endometrial thickness (still in early experimental stages). Following the exposure of endometrial cell samples to a red laser of 635 nm in vitro (in the lab), researchers found the red light-exposed cells had significantly increased in cell number and surface area in comparison to control cells.^lxii In addition, the red light therapy treatment increased the expression of genes known to be important to endometrial receptivity. It was also noted that multiple exposure periods further improve cell proliferation. Overall, this study suggests benefits for endometrial cells following direct exposure to red light therapy. However, this cannot yet be generalized in vivo (in living individuals) until more research is completed; the effects of red light therapy on endometrial function and fertility when applied directly on the pelvic region have not been thoroughly investigated.  

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There are currently no randomized control trials examining the use of red light therapy directly on the body for the improvement of fertility in either males or females. Randomized controlled trials are the gold standard in research when determining the effectiveness of potential treatment. Analysis of the current research suggests that the use of red light therapy may potentially enhance the quality of both oocytes and sperm cells and increase endometrial cell receptivity in a laboratory setting, but there remains a lack of research supporting its actual clinical effectiveness.  

Is red light therapy safe? Side effects of red light therapy

Red light therapy is an emerging technology in the field of fertility, and additional research is required to fully examine the safety, effectiveness, and both short-term and long-term effects.  

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Studies have investigated the safety of red light therapy for the treatment of other medical issues, such as musculoskeletal and dermatological conditions.^lxiii,^lxiv Visible light therapies, such as red light therapy, do not utilize harmful, cancer-causing light rays such as UV. Further, there is no clinical trial data linking red light therapy with any significant negative side effects.^lxv However, it is worth noting that this has not been fully investigated directly in female pelvic structures or male genitalia.

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While many devices are available on the market for at-home use, buyers should be aware of red light therapy devices marketed as “FDA approved,” as the FDA does not approve these devices. Consumers, especially males, should be cautious of red light therapy devices that produce heat. It is critical for sperm production that testicular temperature remains approximately two to three degrees Celsius below body temperature; therefore, heat emitting red light devices may have a negative impact on spermatogenesis and overall male fertility.^lxvi  

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It has been suggested that one potential unwanted side effect of red light therapy is DNA damage due to reactive oxygen species (ROS) that are generated in the process. For example, 630 nm laser light stimulation has been shown to increase production of ROS such as hydrogen peroxide (H₂O₂) in mouse sperm.^lxvii At high levels, reactive oxygen species can damage the DNA inside a cell and thus researchers have suggested that this should be investigated further. One 2017 study showed that oxidative damage was not increased in sperm exposed to 633 nm red laser light in order to improve sperm motility. The study analyzed oxidative damage in the sperm DNA and found no evidence that irradiation caused DNA damage.^lxviii

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Similarly, researchers reported in 2023 that red light treatment of human PCOS oocytes undergoing in vitro maturation experienced a decrease in ROS levels, accompanied by a decrease in cell-degradation related gene expression.^lxix  

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A study in Egypt using cultured endometrial cells examined potential negative effects of sustained laser exposure.^lxx Findings showed that the higher laser dosage and increased laser exposure time (20 minutes vs. 10 minutes) resulted in thermal damage to endometrial cells. While this study was conducted in a lab using cultured endometrial cells, findings from this experiment further emphasize the importance of caution of both laser strength and exposure time when considering red light therapy.^lxxi

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Given the variability of study results to date, individuals seeking red light therapy for fertility benefits should remain cautious, as various companies are marketing red light therapy and associated devices without strong peer-reviewed evidence to back them up.  

Timing and logistics

Limited fertility providers may offer red light therapy add-ons for fertility treatment, but it is not common and lacks evidence of effectiveness (discussed above).  It may also be offered by medical spas and at acupuncture clinics. Medical LED light therapy devices are also available for purchase for at-home use, though there is very little evidence as to their effectiveness.  

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A specific type of red light therapy, called laser acupuncture, can be offered the day of embryo transfer.^lxxii This therapy includes the use of a small pen-like device that emits a low-level red light laser. Treatment can be focused on points often targeted with regular acupuncture such as the ears, abdomen, arms, legs, and top of the head for approximately half a minute per area.^{lxxiii, lxxiv} This treatment is painless and can be offered before the transfer, after the transfer, or both. The goal of laser acupuncture is to increase blood flow to the uterus to increase implantation success.^lxxv

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There are larger red light (and near red light) emitting devices which are available for focusing on the abdominal/pelvic area to focus treatment on the uterus and/or ovaries. Therapy sessions are usually recommended for a duration of 20 minutes.^lxxvi,lxxvii Because red light therapy is believed to impact cellular activity by increasing mitochondrial production of ATP, there is theoretical potential for red light therapy to improve egg quality which would increase fertility. Additionally, women may also potentially benefit from red light therapy by promoting blood flow to support embryo implantation.^{lxxviii, lxxix}

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Red light therapy for male fertility may be offered using similar devices at acupuncture clinics, which directs red light to the cells located in the testicle which stimulate sperm production, known as Sertoli cells. For men seeking improved sperm-related benefits, red light therapy sessions could theoretically be beneficial up to three months in advance for couples seeking assisted reproductive technologies including IUI or IVF. While men produce sperm every day, the period it takes to produce mature, motile sperm from immature spermatogonia is approximately 3 months.^lxxx

Overall, the lack of substantial clinical data remains a concern in research for this type of therapy, and its effectiveness for enhancing egg quality and male fertility lacks robust peer-reviewed research. Furthermore, recommendations from medical societies and organizations have also not endorsed the use of red light therapy.

Conclusion

In summary, red light therapy may hold promise in enhancing male and female fertility by potentially improving mitochondrial energy production, blood flow, and reducing oxidative stress. However, the available peer-reviewed research in this area is minimal. While preliminary research is encouraging, further clinical studies are necessary to confirm its theoretical effectiveness. Although there are no studies indicating negative side effects of red light therapy, additional studies are required to address any potential risks and to ensure overall general safety. Patients reading about red light therapy on blogs, social media, or other non-scientific sources should be weary of any claims that red light therapy for fertility is supported by clinical research. Given the lack of evidence, and lack of support from medical societies, individuals considering red light therapy for fertility should consult with medical professionals before using red light therapy during their fertility journey.

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Sexually transmitted infections (STIs) can potentially damage the reproductive organs and lead to infertility. It is crucial for sexually active individuals, regardless of age, gender, or sexual orientation to undergo STI testing regularly in order to proactively take responsibility for their sexual health. Early diagnosis and management of STIs are essential for avoiding long-term harm to reproductive organs and for maintaining fertility. This article covers what STIs are, how they may impact fertility, and options for their prevention and treatment.

Though a vasectomy was formerly considered a permanent sterilization procedure, modern developments have made reversal possible. This article will outline the various procedures for reversing a vasectomy and the likelihood of success in restoring fertility, including a comparison to alternative fertility options.

Menopause is a natural process all women will eventually go through as they reach middle age. During menopause, the ovaries stop releasing eggs, menstrual periods become less frequent and eventually cease, and hormones such as estrogen and progesterone decrease. While menopause marks the end of fertility, there is still a chance to become pregnant during menopause - either naturally or through fertility treatments.

Individuals who are transgender or transitioning face unique issues regarding fertility, family building, and fertility preservation. The term transgender describes individuals who do not identify with the sex they were assigned at birth. Gender identity is complex and exists on a spectrum. While some transgender people identify with a gender different than the sex they were assigned at birth (often referred to as genetic or biological sex), others do not identify as either of the traditional binary genders.  

Transgender men are individuals who were assigned female sex at birth but identify as male, while transgender women are those who were assigned male sex at birth and identify as female. Some transgender individuals prefer to be identified only as men/male or women/female, dropping the term transgender. Others prefer the terms trans man or trans woman. In this article we will discuss options for creating a family as a transgender individual as well as for those who are undergoing gender transition, and will use trans or transgender terminology for conciseness even as we recognize the differences in preferred language. We will also discuss pregnancy, the delivery process, and aspects of the postpartum course for these individuals.  

Transgender parenthood is fairly common. According to the U.S. Transgender Population Health Survey, 19 percent of transgender respondents were parents.ⁱ

ERA, which stands for endometrial receptivity analysis (previously known as endometrial receptivity array), is a diagnostic tool intended to determine how “receptive” the maternal uterine lining (endometrium) is towards implantation of a transferred embryo.^i,ii ERA evaluates the expression of genes involved in endometrial receptivity during the window of implantation (WOI). These results are then used to determine whether a patient should have a frozen embryo transfer with standard timing, or if timing needs to be adjusted to account for a displaced WOI, a process known as personalized embryo transfer (pET).

Acupuncture is a type of complementary medicine involving the insertion of small needles into specific acupuncture points in the body. It is believed to work by stimulating the nervous system, which can then affect muscles and glands. It has been estimated that over 30 percent of women undergoing fertility treatment will access an alternative medical approach such as acupuncture during their treatment.ⁱ  Fertility acupuncture gained popularity in North American around 2009. Since then, research of varying quality has been conducted to assess the role of acupuncture in both male and female fertility. Its effectiveness in helping improve fertility, especially with respect to IVF success rates, remains unclear.

This article focuses on sperm retrieval procedures, which are procedures that remove sperm from the testicles for the purpose of fertilizing an oocyte (egg). This may be used for men with no sperm in the ejaculate (azoospermia), but that still produce sperm in the testes.

There are two main types of techniques for surgical sperm retrieval: aspiration and extraction. Sperm aspiration involves using a needle to remove (aspirate) sperm from the epididymis or the testes. Sperm extraction takes a sample of the tissue, known as a biopsy, to collect the sperm. There are also different variations or subtypes of these procedures, as well as non-surgical approaches for those with ejaculation limitations.

Klinefelter syndrome (KS) is a genetic condition whereby a male is born with an extra X chromosome. This condition often impacts fertility in addition to potentially other areas related to health and development, though having this condition does not necessarily mean a person cannot have biological children. By understanding this condition's symptoms, causes, risks, and treatments, those with KS can navigate treatment options.

Pregnancy loss can be devastating under any circumstances, but repeated losses can be particularly difficult to deal with. Recurrent pregnancy loss is defined as having two or more miscarriages. Overall, the risk of pregnancy loss is approximately 25 percent, meaning 1 in 4 recognized pregnancies end in loss. The risk of having two or three pregnancy losses in a row is approximately 2.25 percent and 1 percent respectively. After three consecutive losses, the risk of another pregnancy loss rises to around 40 percent.ⁱ  

In order to understand recurrent pregnancy loss (RPL), it is important to know the potential causes of RPL and what tests and treatments are available to help women experiencing the devastating impact of recurrent miscarriage.

A dilation and curettage (D&C) is a surgical procedure that is used to remove tissue from the uterus, and while it is performed for a variety of reasons including diagnostic purposes, it is typically used following a miscarriage or for elective termination of a pregnancy. An understanding of what to expect before, during, and after a D&C is beneficial for navigating this procedure, as well as to learn about potential risks and alternative treatments.

Because hypothyroidism can play a role in infertility, a woman going through in vitro fertilization (IVF) should be aware of the symptoms of hypothyroidism and possible treatments.

Infertility is recognized as a disease by the World Health Organization (WHO), as well as many other professional societies, including the American Medical Association (AMA), the American Society for Reproductive Medicine (ASRM), and the European Society of Human Reproduction and Embryology (ESHRE).^i,ii,iii,iv Estimates of infertility frequency vary worldwide, and even differ depending on the way data is collected. Prevalence is the term used to describe how common a disease/condition is in a particular population. According to the US National Survey of Family Growth, approximately 19.4 percent of married heterosexual women aged 15-49 years have experienced infertility.^v Estimates in the UK population for a similar population were 12.5 percent.^vi Some studies indicate that the prevalence of male infertility is approximately 10-15 percent, but these estimates may not be accurate due to the lack of good quality evidence.^vii

Egg donation is a process in which a fertile woman donates her eggs (oocytes) to another individual or couple who want to conceive a baby. There are a number of steps involved in not only the decision to use donor eggs, but then to move forward once that decision has been made. For anyone considering using donor eggs, it is important to understand the details around how egg donation works, how to find an egg donor, and what success looks like in this type of fertility journey.

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Embryo implantation is a complex process and a significant step towards achieving a viable pregnancy. Implantation requires good quality embryos (both genetically and structurally normal), a receptive endometrium, and complex communication between the embryo and the uterine lining.ⁱ The term “implantation failure” describes the lack of a positive pregnancy test (increased human chorionic gonadotropin (hCG) levels) or the lack of an intrauterine pregnancy seen on ultrasound following in vitro fertilization (IVF) and embryo transfer.ⁱⁱ Recurrent implantation failure (RIF) is sometimes called repeated implantation failure, and the terms can be used interchangeably.

A miscarriage is the loss of a clinically confirmed pregnancy. For women hoping to conceive, it is important to have accurate information regarding pregnancy loss including prevalence, common causes, warning signs, and management options. An understanding of what to expect after miscarriage and what physical and emotional factors should be considered before trying to conceive again can also be highly beneficial.

Asherman’s syndrome is a rare condition defined by the formation of scar tissue in the uterine cavity. It does not have a genetic predisposition and can affect any woman, with a potential impact on fertility. Most cases develop in women who have undergone uterine surgeries. If a woman has received an Asherman’s syndrome diagnosis and is concerned about its impact on her fertility, it is beneficial to understand the symptoms, causes, and range of potential reproductive outcomes.

Monosomy X is a chromosome abnormality that occurs randomly during fertilization and affects only females. Also known as Turner syndrome (TS), this is a genetic condition that if present in a fetus causes significantly increased risk for miscarriage and prenatal complications, like heart defects. After birth, individuals with Turner syndrome are at increased risk for growth issues, learning disabilities, and infertility as adults. Fortunately, with proper early intervention and counseling on reproductive options and risks, women with TS may go on to have successful pregnancies.

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Polycystic ovary syndrome (PCOS) is a condition that is often associated with having a negative impact on a woman's ability to conceive. This syndrome is characterized by a range of symptoms, from unwanted hair growth to challenges when trying to conceive, and can be difficult to diagnose and treat.