History Of Assisted Reproductive Technology Research Articles

Risk Factors and Clinical Patterns of Infertility in Couples: A Hospital-based Cross-sectional Study in Southern Khyber Pakhtunkhwa, Pakistan

Infertility is ranked as the fifth-leading cause of disability in the world's population under 60 years old, according to the World Health Organization, affecting an estimated 80 million people worldwide. This reproductive health disorder can be caused by various factors, including structural, biological, and congenital issues, as well as acquired and environmental variables. To investigate the prevalence and potential risk factors of infertility, a hospital-based cross-sectional study was conducted in district Kohat, Pakistan, from January to May 2021. A total of 120 infertile couples were recruited from the outpatient center at Liaquat Memorial Hospital, and their medical files were reviewed, followed by face-to-face interviews with both partners of each couple. Of the participants, 47.5% were suffering from primary infertility, while 52.5% were affected by secondary infertility. Female infertility was the most common form of infertility, affecting 49.16% of couples, followed by male infertility (15.83%), couples with both partners facing infertility issues (8.33%), and unspecified infertility (26.66%). The most frequent causes of male and female infertility were erection issues (48.27%) and hormonal imbalances (40.57%), respectively. Additionally, 46.34% of couples reported stress and anxiety, and 14.16% had a history of assisted reproductive technology. Furthermore, 18.3% of couples had a family history of infertility, with 77.27% of those affected being infertile females. Infertile couples were also assessed based on potential risk factors, including age difference, age at menarche, occupation, smoking, and BMI. These findings may aid in identifying the factors contributing to infertility among the population.

Assisted reproductive technology, risk of gestational diabetes, and perinatal outcomes in singleton pregnancies.

To evaluate the impact of assisted reproductive technology (ART) on the risk of gestational diabetes mellitus (GDM) in single pregnancies. We retrospectively collected clinical and anthropometric data of 219ART- and 256 age- and body mass index (BMI)-matched women with spontaneous conception screened for GDM. The primary outcome was to evaluate GDM prevalence in ART women. There were no differences in age, BMI, and family history of diabetes in the two groups of women. ART-women were more frequently primiparous, whereas the prevalence of previous GDM was higher in SC-women. The prevalence of GDM in thewhole cohort was 36.1% and was higher in ART-women (52.3% vs. 23.4%; p<0.0001). In the whole cohort, on multivariate analysis, family history of diabetes (OR 1.67; 95% CI: 1.03-2.69), previous GDM (OR 7.05; 95% CI: 2.92-17.04), pre-pregnancy obesity (OR 2.72; 95% CI 1.21-6.13), and ART (OR 4.14; 95% CI 2.65-6.48) were independent risk factors for GDM. Among ART-women, age over 40years was associated with GDM. Preterm delivery was more common in ART-women; gestational week at delivery, birth weight, ponderal index, and Apgar score were lower in ART-women than in SC-women, both in the whole cohort and in GDM women. Among women undergoing ART treatment, at least one in two develops GDM. ART appears to be an independent risk factor for GDM in single pregnancies, particularly above the age of 40. ART treatment seems to be associated with an increased rate of preterm delivery and lower neonatal birth weight and Apgar score, especially in GDM women. The study was not registered as it is an observational retrospective evaluation.

Perinatal and neonatal characteristics of Prader-Willi syndrome inJapan.

Prader-Willi syndrome (PWS) is suspected at birth if extreme hypotonia, difficulty in feeding, hypogonadism, and failure to thrive are present. Genetic diagnosis of PWS can generally be made within the first few months of life; however, a delayed diagnosis of PWS is frequently reported. Although the clinical characteristics of perinatal and neonatal patients with PWS have been reported, there are no such reports on the clinical characteristics of these patients in Japan. This retrospective, single-center study involved 177 Japanese patients with PWS and their medical data regarding the perinatal and neonatal periods were evaluated. The median maternal age at birth was 34 years; 12.7% of the mothers had a history of assisted reproductive technology (ART). Of the mothers, 13.5% reported polyhydramnios and 4.3% had oligohydramnios. Decreased fetal movement during pregnancy was reported by 76% of the mothers. A total of 60.5% of patients were born by cesarean section. Genetic subtypes included deletions (66.1%), uniparental disomy (31.0%), imprinting defects (0.6%), and other or unknown subtypes (2.3%). The median birth length was 47.5 cm and the median birthweight was 2476 g. Of the 160 patients, 14 (8.8%) were classified as small for gestational age. Most patients had hypotonia (98.8%), and 89.3% required gavage feeding at birth. Breathing problems, congenital heart disease, and undescended testis were noted in 33.1%, 7.0%, and 93.5% of patients, respectively. In our study, higher rates of ART, polyhydramnios, decreased fetal movements, cesarean section, hypotonia, feeding difficulties, and undescended testis were observed in PWS.

Abstract 13451: Cardiovascular Complications During Delivery Admissions Associated With Assisted Reproductive Technology: A National Inpatient Sample Analysis (2008-2019)

Introduction: Persons who conceived through Assisted Reproductive Technology (ART) have an increased risk of obstetric-associated complications. Hypothesis: ART is associated with increased acute cardiovascular (CV) complications during delivery admissions. Methods: We used data from the National Inpatient Sample (2008-2019) while utilizing ICD-9 or ICD-10 codes to identify delivery hospitalizations and ART procedure. Results: A total of 45,867,086 weighted delivery cases were identified, of which 0.24% were among individuals who conceived through ART (n=108,542). Persons with an ART history were older at the time of delivery (median 35 vs. 28 years, p&lt;0.01) and had higher prevalence of hypertension, gestational diabetes, and dyslipidemia (all, p&lt;0.01). After adjustment for age, race/ethnicity, comorbidities, multiple gestation, insurance, and income, ART remained an independent predictor of peripartum CV complications including preeclampsia (aOR 1.48 [1.45-1.51], p&lt;0.01), heart failure (aOR 1.94 [1.10-3.40], p&lt;0.01), and cardiac arrhythmias (aOR 1.39 [1.30-1.48], p&lt;0.01) compared to natural conception. Likewise, the risk of acute kidney injury (aOR 2.57 [2.25-2.92], p&lt;0.01), stroke (aOR 1.57 [1.23-2.01], p&lt;0.01), pulmonary edema (aOR 2.29 [2.02-2.61], p&lt;0.01), and venous thromboembolism (aOR 1.92 [1.63-2.25], p&lt;0.01) were higher with ART. However, higher odds of developing peripartum cardiomyopathy or acute coronary syndrome were not associated with ART. Length of stay (3 vs. 2 days, p&lt;0.01) and cost of hospitalization ($5,903 vs. $3,922, p&lt;0.01) were higher for deliveries among persons with history of ART. Conclusions: Persons who conceived with ART had higher risk of preeclampsia, heart failure, cardiac arrhythmias, pulmonary edema, AKI, stroke, and VTE during their delivery hospitalizations. This may in part contribute to increased resource utilization seen in patients conceiving with ART

Cardiovascular Complications During Delivery Admissions Associated With Assisted Reproductive Technology (from a National Inpatient Sample Analysis 2008 to 2019)

Women who conceive through assisted reproductive technology (ART) have a known increased risk of obstetric complications. However, whether ART is also associated with higher risk of developing cardiovascular complications during delivery admissions has not been well established. We used data from the National Inpatient Sample (2008 to 2019) and used the International Classification of Diseases codes to identify delivery hospitalizations and ART procedures. A total of 45,867,086 weighted delivery cases were identified, of which 0.24% were among women who conceived through ART (n=108,542). Women with an ART history were older at the time of delivery (median 35 vs 28years, p <0.01) and had a higher prevalence of hypertension, gestational diabetes, and dyslipidemia (all, p <0.01). After adjustment for age, race/ethnicity, co-morbidities, multiple gestation, insurance, and income, ART remained an independent predictor of peripartum cardiovascular complications, including pre-eclampsia/eclampsia (adjusted odds ratio [aOR] 1.48, 95% confidence interval [CI] 1.45 to 1.51), heart failure (aOR 1.94, 95% CI 1.10 to 3.40), and cardiac arrhythmias (aOR 1.39, 95% CI 1.30 to 1.48), compared with natural conception. Likewise, the risk of acute kidney injury (aOR 2.57, 95% CI 2.25 to 2.92), ischemic stroke (aOR 1.73, 95% CI 1.24 to 2.43), hemorrhagic stroke (aOR 1.63, 95% CI 1.27 to 2.11), pulmonary edema (aOR 2.29, 95% CI 2.02 to 2.61), and venous thromboembolism (aOR 1.92, 95% CI 1.63 to 2.25) were higher with ART. However, odds of developing peripartum cardiomyopathy or acute coronary syndrome were not associated with ART. Length of stay (3 vs 2 days, p <0.01) and cost of hospitalization ($5,903 vs $3,922, p <0.01) were higher for deliveries among women with a history of ART. In conclusion, women who conceived with ART had higher risk of pre-eclampsia, heart failure, arrhythmias, stroke, and other complications during their delivery hospitalizations. This may, in part, contribute to their increased resource utilization seen.

Effectiveness and safety of intrauterine insemination vs. assisted reproductive technology: emulating a target trial using an observational database of administrative claims

To compare the effectiveness and safety of 1 cycle of assisted reproductive technology (ART) vs. 3 cycles of intrauterine insemination (IUI). Target trial emulation using observational data. A healthcare claims database (2011-2015). The patients were 29,021 women aged 18-45 years with an infertility diagnosis and no history of IUI or ART within the past 12 months. One ART cycle immediately, with no more cycles of ART or IUI within the next 4 months; or 1 IUI cycle immediately, with 2 additional consecutive cycles of IUI within the next 4 months unless pregnancy occurred. Live births, multiple births, congenital malformations, preterm births, small-for-gestational-age newborns, large-for-gestational-age newborns, admission to neonatal intensive care unit (NICU), gestational diabetes, preeclampsia, and gestational hypertension. The probability of live birth was 27.3% for ART and 26.3% for IUI. The observational analogue of per-protocol risk difference (95% confidence interval) for ART compared with IUI was 1.0% (-0.1%, 2.2%) for live births, 4.3% (3.7%, 4.9%) for multiple births, 3.4% (2.8%, 4.0%) for preterm births, 1.5% (0.9%, 2.1%) for NICU admissions, and 0.6% (0.2%, 1.0%) for gestational diabetes. The risk differences for the other outcomes were <0.5%. The results of the 2 strategies were similar in women ≤40 years, but in women >40 years the probability of live birth was greater for ART (14.4%) than for IUI (7.4%). Compared with 3 cycles of IUI, 1 cycle of ART was estimated to have a similar probability of live birth but slightly higher risks of multiple gestations, preterm births, and NICU admissions.

From lessons on the long-term effects of the preimplantation environment on later health to a "modified ART-DOHaD" animal model.

BackgroundAt its earliest stages, mammalian embryonic development is apparently simple but vulnerable. The environment during the preimplantation period, which only lasts a couple of days, has been implicated in adult health, extending to such early stages the concept of the developmental origin of health and disease (DOHaD).MethodsIn this review, we first provide a brief history of assisted reproductive technology (ART) focusing on in vitro culture and its outcomes during subsequent development mainly in mice and humans. Further, we introduce the “MEM mouse,” a novel type 2 diabetes mouse model generated by in vitro culture of preimplantation embryos in alpha minimum essential medium (αMEM).Main findingsThe association between ART and its long‐term effects has been carefully examined for its application in human infertility treatment. The “MEM mouse” develops steatohepatitis and kidney disease with diabetes into adulthood.ConclusionThe close association between the environment of preimplantation and health in postnatal life is being clarified. The approach by which severe mouse phenotypes are successfully induced by manipulating the environment of preimplantation embryos could provide new chronic disease animal models, which we call “modified ART‐DOHaD” animal models. This will also offer insights into the mechanisms underlying their long‐term effects.

Comprehensive meta-analysis reveals association between multiple imprinting disorders and conception by assisted reproductive technology.

To determine whether a history of conception by assisted reproductive technology (ART) is associated with occurrence of one or more imprinting disorders of either maternal or paternal origin. We implemented a systematic review of scholarly literature followed by comprehensive meta-analysis to quantitatively synthesize data from reports relating to use of ART to occurrence of any imprinting disorder of humans, including Beckwith-Wiedemann (BWS), Angelman (AS), Prader-Willi (PWS), and Silver-Russell (SRS) syndromes, as well as transient neonatal diabetes mellitus (TNDB) and sporadic retinoblasoma (RB). The systematic review identified 13 reports presenting unique data from 23 studies that related conception following ART to occurrence of imprinting disorders. Multiple studies of four disorder were identified, for which meta-analysis yielded the following summary estimates of associations with a history of ART: AS, summary odds ratio (sOR) = 4.7 (95% confidence interval (CI) 2.6-8.5, 4 studies); BWS, sOR = 5.8 (95% CI 3.1-11.1, 8 studies); PWS, sOR = 2.2 (95% CI 1.6-3.0, 6 studies); SRS, sOR = 11.3 (95% CI 4.5-28.5, 3 studies). Only one study reported on each of TNDB and RB. Published data reveal positive associations between history of ART conception and each of four imprinting disorders. Reasons for these associations warrant further investigation.

Does Bariatric Surgery Improve Assisted Reproductive Technology Outcomes in Obese Infertile Women?

Little is known about the impact of bariatric surgery on obese infertile women seeking an assisted reproductive technology. All obese women with a history of assisted reproductive technology (ART) failure that underwent ART treatment cycles both prior to and following bariatric surgery were included. ART outcomes were compared evaluating the duration and dose of gonadotrophins used; the measurement of day 3 FSH; the anti-mullerian hormone dosage; the number of follicles >15mm; the number of retrieved and fertilized oocytes; the number of metaphase II, metaphase I and germinal vesicle oocytes; the number of embryos obtained; the number of top-quality oocytes and embryos; the number of transferred embryo; the pregnancy rate and the live birth rate. Forty women were included. The total number of gonadotropin units required and in the length of stimulation following bariatric surgery decreased (p=.001), with an increase of the number of follicles ≥15mm (p=.005), of retrieved oocytes (p=.004), of top-quality oocytes (p=.001) and metaphase II oocytes (p=.008). More oocytes were fertilized (4.2±1.7 vs 5.3±2.4; p=.02). After surgery, we have registered also a better number of top-quality embryos (0.5±0.6 vs 1.1±0.9; p=.003). Pregnancy rate following the bariatric surgery increased to 15/40 (37.5%) (p<.001), and live birth rate (LBR) increased to 14/40 (35%) in the post-surgery group (p<. 001). Although additional research would be useful to draw definitive conclusion, our results appear to be encouraging enough to suggest the use of bariatric surgery in obese infertile women seeking an ART treatment.

Should a history of assisted reproductive technology be another consideration when assessing cardiovascular risk?

Should a history of assisted reproductive technology be another consideration when assessing cardiovascular risk?

History of Assisted Reproductive Technology and Chlamydia Trachomatis Infection in Pregnancy.

Background and MethodsTo identify whether or not a history of assisted reproductive technology (ART) is associated with the low incidence of Chlamydia trachomatis (CT) infection in pregnant women, we reviewed the obstetric records of the Japanese women aged 35 - 42 years.ResultsThe prevalence of CT in the pregnancies without ART was 1.1% (28/2,632) using nucleic acid amplification tests, while it was zero in the pregnancies conceived by ART (0/364, P = 0.049 by the X2 test).ConclusionsA history of ART seemed to be a negative risk factor for CT infection in pregnant women.

Prenatal diagnosis of hypomethylation at KvDMR1 and Beckwith–Wiedemann syndrome in a pregnancy conceived by intracytoplasmic sperm injection and in vitro fertilization and embryo transfer

ObjectiveWe report prenatal diagnosis of hypomethylation at KvDMR1 and Beckwith–Wiedemann syndrome (BWS) in a pregnancy conceived by intracytoplasmic sperm injection and in vitro fertilization and embryo transfer. Case reportA 34-year-old, primigravid woman was referred to the hospital at 21 weeks' gestation because of advanced maternal age and an isolated omphalocele in the fetus. Her husband had the fertility problem of oligospermia. This pregnancy was achieved by intracytoplasmic sperm injection and in vitro fertilization and embryo transfer. Prenatal ultrasound revealed a 2.1 cm × 1.6 cm isolated omphalocele. The woman underwent amniocentesis. Array comparative genomic hybridization and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) were applied to the DNA extracted from the uncultured amniocytes. Conventional cytogenetic analysis and high-resolution melting analysis were performed on cultured amniocytes. Array comparative genomic hybridization revealed no genomic imbalance. MS-MLPA analysis revealed H19DMR(IC1) normal methylation and KvDMR1(IC2) hypomethylation. Conventional cytogenetic analysis revealed a karyotype of 46,XX. High-resolution melting analysis using a methylation-specific polymerase chain reaction assay confirmed normal methylation at H19DMR(IC1) and hypomethylation at KvDMR1(IC2). The altered methylation status at 11p15.5 and the phenotype of omphalocele were consistent with the diagnosis of BWS. ConclusionIn case of prenatally detected omphalocele associated with an obstetric history of assisted reproductive technology, a differential diagnosis of BWS should be considered. Methylation assays such as MS-MLPA and methylation-specific polymerase chain reaction using uncultured amniocytes are useful for rapid diagnosis of BWS under such circumstances.

History of assisted reproductive technology for treating infertility in Bukovyna

Historical facts of the introduction of assisted reproductive technologies for the treatment of infertility in Bukovуna are presented in the paper.

The Effect of Assisted Reproductive Technologies on Gynecological Cancer: Report of Our Experiences and Literature Review

Introduction: Infertility is as an important and common problem in couples necessitating assisted reproductive technology (ART) or drug therapy. Infertility is known as a risk factor for ovarian, breast and endometrial cancer. We aimed on evaluation of the history of primary infertility and previous ART in patients with the above-mentioned cancers. Material and method: In this retrospective study we evaluated all of the risk factors in patients with breast cancer, ovarian cancer and endometrial cancers who referred to the Gynecological Oncology Clinic in Shahid Sadoughi Hospital in Yazd, Iran from 2002 to 2012. We also investigated the history of primary infertility and ART in these patients before diagnosis of cancers. Results: We gathered data from 92 patients with endometrial cancer, 84 patients with advanced epithelial ovarian cancer and 113 patients with breast cancer. There was history of infertility in 39.1% of patients with endometrial cancer who were obese (body mass index, BMI&gt;29) and in 18.8% of patients with endometrial cancer and normal body mass index (BMI=25-29). ART had been performed in 7.3% of all patients with endometrial cancer. In patients with epithelial ovarian cancer, infertility was diagnosed in 28.4% and ART applied in 14.1%. Clomiphene with or without HCG and HMG was the most common drug used for patients with ovarian cancer. In patients with breast cancer, there was infertility in 16.5% and ART performed in 7.3%. Conclusion: Although infertility was present as an important and fairly common risk factor in some patients with endometrial, ovarian and breast cancer, but some other factors may be more important, including age, BMI and the etiology of infertility. Finding the association between ART and gynecological cancers needs long cohort studies with follow-up of infertile women who get the ART or drug therapy for over 15-20 years. We think BMI and age (in addition to infertility and ART) are contributing factors for development of gynecological cancers.

Gone and forgotten: where has the “literature” gone?

Gone and forgotten: where has the “literature” gone?

Evolving Role of Assisted Reproductive Technologies

During the past 3 decades, staggering advances have been made in the field of assisted reproductive technology (ART). This review provides an overview of the history of ART, current ART practices, and future directions within the field.

Unexplained Infertility Treated with Acupuncture and Herbal Medicine in Korea

We aim to determine the safety and effectiveness of a standard therapeutic package of Korean medicine for the treatment of unexplained infertility in a cross-section of women who sought treatment at an integrative hospital in Seoul, Korea. Infertility affects more than 1.2 million women in the United States alone. Treatment options for infertility vary, yet the barriers of invasiveness, cost, and access inhibit treatment use for many women. Alternative medical approaches exist for this indication, and sustain certain popularity. Therefore, we systematically studied a standard therapeutic package of Korean medicine to treat unexplained infertility in women. Female participants included in this observational study met inclusion criteria before receiving a set of treatments including herbal medicine, acupuncture, and moxibustion. A study physician screened each patient in accordance with inclusion criteria, provided study information, and after the patients consented, performed the baseline assessment. Assessments included age, the history of assisted reproductive technology, and duration of infertility. The key outcome measure included the number who achieved pregnancy and any neo-natal morbidity and mortality at follow-up stage for those who got pregnant. Any other adverse events including aggravation of existing symptoms, and the number of dropouts, were recorded. Treatments were supposed to be completed after 6 menstrual cycles between February 2005 and April 2006. One hundred and four (104) women with unexplained infertility were included in this observational study. Participant mean age was 32 years (SD: 2.7), with a range between 26 and 41 years. The median duration of infertility after diagnosis was 33.5 weeks (interquartile range: 20.8-50.3). In total, 41 participants (39.4%) had undergone a mean number of 1.4 (SD: 2.2) assisted reproductive technology treatments prior to joining the study. The number of patients remaining in or achieving pregnancy throughout the 6-month study period was 23 (14 pregnancies), 22.1%. Six (6) participants (4.8%) reported minor adverse events including rash in the face (n = 1), diarrhea (n = 2), dizziness (n = 1), and heartburn (n = 2). Of the 14 pregnancies, there were 10 normal births, and 4 miscarriages; otherwise, no neonatal morbidity/mortality occurred. According to per protocol analysis, 14 pregnancies out of 23 total were achieved by those who remained for the entire six menstruation cycle treatments, yielding a pregnancy rate of 60.9%. The standard therapeutic package for unexplained infertility in women studied here is safe for infants and the treated women, when administered by licensed professionals. While it remains challenging to have the target population complete a 6-month treatment course, during which most patients have to pay out of pocket, the extent of successfully achieved pregnancy in those who received full treatment provides meaningful outcomes, warranting further attention. A future study that includes subsidized treatment costs, encouraging the appropriate compliance rate, is warranted. 194.

In Vitro Maturation of Unstimulated Immature Oocyte for the Treatment of Infertility Women

To evaluate the efficacy of in vitro maturation (IVM) of unstimulated immature oocytes for the treatment of infertility women Prospective observational study Fifty-four cycles of IVM in 40 infertility patients including 26 women with obstinate polycystic ovary syndrome (PCOS), 14 patients with the failed history of assisted reproductive technology (ART) were carried out, 7 cycles were cancelled and the cancel rate was 13%.Transvaginal ultrasound-guided oocyte collection was performed on menstrual cycle day 9∼12 without pretreatment of gonadotropins. The oocytes were cultured in vitro using maturation medium, which consisted of TCM 199 medium supplemented with 20% fetal bovine serum, 0.075IU/mlFSH and 0.1IU/mlHCG. After 24∼48 hrs of culture, the metaphase II stage oocytes were inseminated by intracytoplasmic sperm injection (ICSI). Embryo transfer was performed 2 or 3 days after ICSI. Laser assisted hatching was done before embryo transfer. A total of 857 immature oocytes were obtained with the mean numbers of 18.2 per cycle. and 632 oocytes developed at MII stage (73.7%). A total of 476 oocytes were fertilized by ICSI (75.3%), with a cleavage rate of 91.2%.Embryo transfer was performed in 47 cycles and the mean number of embryos transferred were 4.3 per cycle (range: 2∼6). The mean thickness of endometrial on the day of embryo transfer was 8.9mm. Ninteen clinical pregnancies were obtained, giving a pregnancy rate of 19/54(35.2%) per puncture cycle and 19/47(40.2%) per transfer cycle. IVM of unstimulated immature oocytes for the treatment of women with various causes of infertility especially with obstinate PCOS is a effective alternative method. The clinical pregnancy rate of 40.2% was similar to conventional IVF treatment in our unit.