Patients Of Advanced Reproductive Age Research Articles

Molecular and genetic predictors of ovarian response in vitro fertilization programs

The most effective method of treating infertility is in vitro fertilization, the key element of which is ovarian stimulation. Ovarian response in IVF protocols has varying variability among patients. The ovarian response depends on many factors, but none of these factors has sufficient prognostic ability, and therefore the question of the individual ovarian response during stimulation in IVF programs still remains open, and the association of the ovarian response with polymorphisms of certain genes is being actively studied. The most effective IVF programs are observed among patients of young reproductive age. A decrease in the effectiveness of IVF programs and the appearance of complications is observed in patients of advanced reproductive age. Several types of ovarian response have been identified: poor (it is possible to obtain 3 oocytes), normal (from 4 to 15 oocytes), suboptimal response (less than 7 oocytes) and hyperergic response (more than 15 oocytes). Also, there is a group of patients of various age groups with a paradoxical ovarian response to stimulation. The response of oocytes to hormones can be regulated depending on the expression of receptor genes. FSH receptor (FSHR) polymorphism may explain interindividual variability in ovarian response to stimulation. Genetic screening is determined once and does not depend on endogenous and exogenous factors, while allowing you to adjust the dose of gonadotropins in ovarian stimulation protocols. This review presents current data on the polymorphism of the main genes that regulate the ovarian response in stimulating superovulation in in vitro fertilization programs.

Myomectomy in adult women of reproductive age: a propensity score-matched study for pregnancy rates.

To study whether it is better to perform or not a myomectomy, in terms of surgical and reproductive outcomes in patients of advanced reproductive age, by an observational prospective study in university-affiliated and Community Hospitals. 40years and older patients affected by non-submucous symptomatic uterine fibroids and desiring future fertility were enrolled and treated by laparoscopic intracapsular myomectomy by (LIM) or by open laparotomy (OIM), or by a non-surgical management as control group, while attempting to conceive. The primary outcome measures were fibroid characteristics, pre- and post-surgical parameters, pregnancy achievement; the secondary outcome measures were the spontaneous or ART pregnancy outcomes, eventual week of abortion and type of delivery. Propensity scores have been calculated with logistic regression for binary and continuous variables. 202 patients completed the study: 112 operated by LIM, 40 by OIM and 50 patients as control group. Patients undergoing OIM have a worse surgical outcome than LIM. No difference was seen in pregnancy either after myomectomy or control group during follow-up. In the LIM group, there were 44 pregnancies (39.2%), and in the OIM group, there were 9 (22.5%) and 16 in the control group (32%). The weeks of delivery were statistically greater for the control group versus the surgical groups, with no difference in Apgar score between the 3 groups. Patients aged over 40years did not show substantial differences in reproductive outcome, whether operated or not. Myomectomy in over 40-year-old patients has no detrimental effect on future pregnancy rates and over when compared to expectant management.

P-223 Women aged 40 or older and non-male factor have the same reproductive outcome using intracytoplasmic sperm injection (ICSI) or conventional in vitro fertilization (cIVF)

Abstract Study question Do women aged 40 or older have the same reproductive outcome using ICSI or cIVF when male factor infertility is not present? Summary answer Women aged 40 or older with non-male factor partners achieved similar reproductive outcomes either with ICSI or cIVF. What is known already Although initially proposed to treat couples with severe male factor infertility, ICSI has become the preferred tool to treat patient populations others than initially intended. Many studies and international forums, however, have alerted that its overuse is not free due to its safety, cost and time-consuming concerns. Moreover, it was noted that it does not increase clinical outcomes even in cases of compromised oocyte factor such as poor responder patients or few oocytes retrieved. However, there is still no information regarding its use in the group of patients of advanced reproductive age. Study design, size, duration Retrospective cohort study including 412 women aged 40 or older with non-male factor infertility performing ICSI or cIVF between May 2015 and October 2017. Participants/materials, setting, methods Patients underwent ICSI (n = 109) or cIVF (n = 303) according to medical indication. The decision to use ICSI in non-male factor patients was merely operational, with the objective of evaluating oocyte maturity.Those cycles with own oocytes, non-male factor and fresh embryo transfers were included. Semen samples were considered normal following the World Health Organization fifth edition sperm parameters values, and prepared by density gradient selection. Main results and the role of chance The primary outcome was clinical pregnancy rate. Secondary outcomes included ongoing pregnancy, miscarriage and implantation rates. Statistical significance was denoted by P < 0.05. The mean age of the women were 41.4 in the ICSI group and 41.6 years in the cIVF group, while the mean age for male couple was 43.6 and 41.6 respectively. No differences between ICSI and cIVF groups were observed regarding clinical pregnancy [16.5% (18/109) vs. 20.8% (63/303)], ongoing pregnancy [9.2% (10/109) vs. 7.9% (24/303)], miscarriage [41.2% (7/17) vs. 46,5% (20/43)], and implantation rates [11.3% (17/151) vs. 9.9% (50/506)]. Limitations, reasons for caution These results need confirmation with a bigger population size. As with any retrospective study, the potential for residual confounding exists. Wider implications of the findings These data suggest that ICSI offers no clinical benefit for women aged 40 and older with non-male factor infertility, beyond oocyte maturation classification. Trial registration number not applicable

Gonadotropin-releasing hormone agonist downregulation combined with hormone replacement therapy improves the reproductive outcome in frozen\u2013thawed embryo transfer cycles for patients of advanced reproductive age with idiopathic recurrent implantation failure

BackgroundTo determine whether gonadotropin-releasing hormone (GnRH) agonist downregulation combined with hormone replacement therapy (HRT) can improve the reproductive outcomes in frozen–thawed embryo transfer cycles for older patients (aged 36–43 years) with idiopathic recurrent implantation failure (RIF).MethodsThis retrospective cohort study involved 549 older patients undergoing their third cleavage-stage embryo or blastocyst transfer over a 5-year period (January 2015–December 2020) at Northwest Women’s and Children’s Hospital after in vitro fertilization/intracytoplasmic sperm injection cycles. Patients with known endometriosis or adenomyosis were excluded from the study. The patients were divided into three groups according to the endometrial preparation protocol: the natural cycle (NC) group (n = 65), the HRT group (n = 194), and the GnRH agonist downregulation combined with HRT cycle (GnRH agonist–HRT) group (n = 290). The primary outcome was the live birth rate, and the secondary outcomes were the clinical pregnancy, miscarriage, and ongoing pregnancy rates.ResultsThe live birth rate in the GnRH agonist–HRT group (36.55%) was higher than that in the HRT group (22.16%) and NC group (16.92%) (P < 0.0001). Similarly, a logistic regression model adjusting for potential confounders showed that the live birth rate was higher in the GnRH agonist–HRT group than in the HRT group (odds ratio, 0.594; 95% confidence interval, 0.381–0.926; P = 0.021) and NC group (odds ratio, 0.380; 95% confidence interval, 0.181–0.796; P = 0.010).ConclusionsThe GnRH agonist–HRT protocol improves the live birth rate in frozen–thawed embryo transfer cycles for patients of advanced reproductive age with RIF. We hypothesize that the GnRH agonist–HRT protocol enhances implantation-related factors and promotes optimal endometrial receptivity, leading to an improved live birth rate. These findings are also useful for further investigating the underlying mechanism of the GnRH agonist–HRT protocol in improving the reproductive outcomes for patients of advanced reproductive age with RIF.Trial registrationThis research protocol was approved by the hospital institutional ethics committee (No. 2021002).

Reproductive senescence and energetic metabolism of human luteinized granulosa cells: is it all about ATP? A prospective cohort and critical view

Mitochondria are known to play a key role in the regulation of reproductive capacity. Senescence is known to impair mitochondrial function and, ultimately, cellular energetic metabolism. Therefore, as women age, a deficient energy supply is likely to affect oocyte quality. The analysis of granulosa cells is considered a valuable noninvasive strategy to assess factors implicated in oocyte competence. Thus, we conducted an observational prospective cohort to evaluate the impact of aging on energy production by luteinized granulosa cells (LGCs). The control group comprised 13 young oocyte donors, whereas the comparison group included 13 infertile women over 38 years of age undergoing in vitro fertilization. Women with diseases that could potentially impact mitochondrial function were excluded. No differences were detected in the ATP levels in LGCs from young donors and infertile patients of advanced reproductive age (1.9 ± 0.99 picomoles in the control group vs. 2.1 ± 0.59 picomoles; p-value = .139). Likewise, the ATP levels in our series did not correlate with either oocyte number or maturity. Despite the similar ATP levels in LGCs, an age effect on the bioenergetic status cannot be excluded. Energy metabolism is very complex, and ATP does not seem to be the most important and reliable parameter.

The protective role of the recombinant IL-2 in complex therapy of cystic ovarian endometriosis in patients of advanced reproductive age

Objective: tto estimate the potential of the protective effect of recombinant IL-2 on the ovarian reserve of patients in advanced reproductive age after enucleation of a cystic ovarian endometriosis (COE). Materials and methods : Initially and over a year after laparoscopic ovarian cystectomy using hemostatic material based on oxidized cellulose, 63 patients with a single-sided COE (4-7 cm) were examined, age group: 36-45 years old. The levels of cytokines (IL-6, IL-2, IL-10, TNF), the content of diene conjugates of unsaturated fatty acids, malonic dialdehyde, superoxide dismutase and the level of molecules of average weight were determined in the peritoneal fluid and peripheral blood. The comparative analysis of the ovarian reserve (the antral follicle count (AFC) and the level of Anti-Mullerian hormone (AMH)) was conducted between 32 patients receiving adjuvant dienogest therapy (6 months) with additional administration of recombinant IL-2 and 31 patients receiving only dienogest. Results: When recombinant IL-2 is used in the early postoperative period, AFС (both, in the intact and operated ovary) and the AMH level (later restored to the results of the initial parameters) increase statistically significant. Conclusions: Recombinant IL-2 compensates the initial deficiency of the regulatory cytokine, reduces the proapoptotic effect on ovarian tissue, and activates antioxidant systems. When used in postoperative period of the complex therapy (IL-2 and dienogest), the ovarian reserve remains almost at the initial level, which favors the implementation of reproductive plans and reduces the likelihood of premature menopause.

Past, Present, and Future Strategies for Enhanced Assessment of Embryo's Genome and Reproductive Competence in Women of Advanced Reproductive Age.

Recent advancements in genomic analysis allow testing of an increasing number of genetic features in human preimplantation embryos. Typical single gene mutation and whole chromosomes testing can now be integrated with assessment of mitochondrial DNA and polygenic conditions. Diagnostic expansion into epigenetic and transcriptomic assessment in the near future are potential technological targets which may improve the prognostic outlook of patients of advanced reproductive age and overall in vitro fertilization (IVF) treatment outcomes. In this review, we discuss the technological progress of recent years and their future applications in preimplantation genetic testing in IVF.

Effect of extended oral contraception use on the prevalence of fetal trisomy 21 in women aged at least 35 years.

To study factors influencing the number of ovulations in reproductive life as risk factors for common trisomies. The present observational study examined data from genetic counseling sessions performed at the 1st Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary, between September 1, 2013, and September 1, 2015, and retrieved data on patients of advanced maternal age (≥35years) who had fetal trisomy 21, 18, or 13 confirmed. Consecutive patients of advanced maternal age with genetic amniocentesis-confirmed healthy fetal karyotypes were also included as a control group. Medical record details were confirmed through telephone interviews with patients; the estimated ovulation number was calculated and compared among patients, as were factors contributing to the number of ovulations each patient had. Data from 12776 genetic counseling situations were examined; 35 patients with fetal trisomies and 100 patients in the control group were interviewed. Shorter mean length of oral contraceptive pill use before trisomic pregnancy (P<0.001) and a higher estimated ovulation number (P=0.012) were identified among patients with pregnancies with fetal trisomies. Fewer ovulatory cycles, potentially resulting from longer oral contraceptive pill use, was associated with healthy fetal karyotypes among patients of advanced reproductive age.

Preimplantation Genetic Diagnosis (PGD) for Monogenic Disorders: the Value of Concurrent Aneuploidy Screening

Pre-implantation genetic diagnosis (PGD) has changed the landscape of clinical genetics by helping families reduce the transmission of monogenic disorders. However, given the high prevalence of embryonic aneuploidy, particularly in patients of advanced reproductive age, unaffected embryos remain at high risk of implantation failure or pregnancy loss due to aneuploidy. 24-chromosome aneuploidy screening has become widely utilized in routine in vitro fertilization (IVF) to pre-select embryos with greater pregnancy potential, but concurrent 24-chromosome aneuploidy screening has not become standard practice in embryos biopsied for PGD. We performed a retrospective cohort study of patients who underwent PGD with or without 24-chromosome aneuploidy screening to explore the value of concurrent screening. Among the PGD+aneuploidy-screened group (n=355 blastocysts), only 25.6% of embryos were both Single Gene Disorder (SGD)-negative (or carriers) and euploid; thus the majority of embryos were ineligible for transfer due to the high prevalence of aneuploidy. Despite a young mean age (32.4±5.9y), 49.9% of Blastocysts were aneuploid. The majority of patients (53.2%) had ≥1 blastocyst that was Single Gene Disorder (SGD)-unaffected but aneuploid; without screening, these unaffected but aneuploid embryos would likely have been transferred resulting in implantation failure, pregnancy loss, or a pregnancyaffected by chromosomal aneuploidy. Despite the transfer of nearly half the number of embryos in the aneuploidy-screened group (1.1±0.3 vs. 1.9±0.6, p<0.0001), the implantation rate was higher (75% vs. 53.3%) and miscarriage rate lower (20% vs. 40%) (although not statistically significant). 24-chromosome aneuploidy screening when performed concurrently with PGD provides valuable information for embryo selection, and notably improves single embryo transfer rates.

PP-017 - Using of calcitonin in culture medium can improve embryo development in patients of advanced reproductive age

PP-017 - Using of calcitonin in culture medium can improve embryo development in patients of advanced reproductive age

Chromosomal Abnormalities in Reimplantation Development

Direct testing of the outcome of human female meiosis demonstrated that up over a half of oocytes from IVF patients of advanced reproductive age are aneuploid, originating comparably from meiosis I and meiosis II errors, with potential probability of aneuploidy rescue in an almost half of oocytes with sequential first and second meiotic errors. One fifth of abnormalities originating from meiosis I and II are of complex nature, with nonrandom distribution of chrmomatid/chromosome (10:1 ratio), and missing/extra chromotid (chromosome) errors (2:1 ratio). The data also demonstrate the relationship between embryo viability and meiotic origin of chromosomal errors, affecting their clinical impact on preimplantation and post-implantation development

First systematic experience of preimplantation genetic diagnosis for single-gene disorders, and/or preimplantation human leukocyte antigen typing, combined with 24-chromosome aneuploidy testing

To study the feasibility, accuracy, and reproductive outcome of 24-chromosome aneuploidy testing (24-AT), combined with preimplantation genetic diagnosis (PGD) for single-gene disorders (SGDs) or human leukocyte antigen (HLA) typing in the same biopsy sample. Retrospective study. Preimplantation genetic diagnosis center. A total of 238 PGD patients, average age 36.8 years, for whom 317 combined PGD cycles were performed, involving 105 different conditions, with or without HLA typing. Whole-genome amplification product, obtained in 24-AT, was used for PGD and/or HLA typing in the same blastomere or blastocyst biopsy samples. Proportion of the embryos suitable for transfer detected in these blastomere or blastocyst samples, and the resulting pregnancy and spontaneous abortion rates. Embryos suitable for transfer were detected in 42% blastocyst and 25.1% blastomere samples, with a total of 280 unaffected, HLA-matched euploid embryos detected for transfer in 212 cycles (1.3 embryos per transfer), resulting in 145 (68.4%) unaffected pregnancies and birth of 149 healthy, HLA-matched children. This outcome is significantly different from that of our 2,064 PGD cycle series without concomitant 24-AT, including improved pregnancy (68.4% vs. 45.4%) and 3-fold spontaneous abortion reduction (5.5% vs. 15%) rates. The introduced combined approach is a potential universal PGD test, which in addition to achieving extremely high diagnostic accuracy, significantly improves reproductive outcomes of PGD for SGDs and HLA typing in patients of advanced reproductive age.

Sequential protocol with urinary-FSH/recombinant-FSH versus standard protocol with recombinant-FSH in women of advanced age undergoing IVF

A stimulation protocol mimicking the physiological pattern of FSH release may improve IVF outcome in women of advanced age. Urinary-FSH delivers a wider range of isoforms including the most acidic produced during the early follicular phase when oestradiol level is low, a common condition in women of advanced reproductive age. We hypothesized that a stimulation protocol using urinary-FSH during the early follicular phase and then shifting toward recombinant-FSH may improve oocyte quality and pregnancy rate in 35–40 years old patients in IVF program. A retrospective study was performed: after a standard down-regulation with GnRH-analogue, 115 women underwent stimulation with urinary-FSH for 6 days according to a step-down approach and then shifting to recombinant-FSH (group A), 115 women underwent a stimulation protocol with only recombinant-FSH (group B). Days of stimulation were lower in group A than in group B, a higher proportion of MII oocytes and of grade 1 embryos, higher implantation rate and pregnancy rate were observed in group A versus group B. We conclude that a sequential protocol using urinary-FSH in the early days of stimulation and subsequently recombinant-FSH may improve the IVF outcome in patients of advanced reproductive age.

Differential expression patterns and clinical significance of estrogen receptor-α and β in papillary thyroid carcinoma

BackgroundThe incidence of papillary thyroid cancer (PTC) is markedly higher in women than men during the reproductive years. In vitro studies have suggested that estrogen may play an important role in the development and progression of PTC through estrogen receptors (ERs). This study aimed to investigate the expression patterns of the two main ER subtypes, α and β1 (wild-type ERβ), in PTC tissue and their clinical significance.MethodsImmunohistochemical staining of thyroid tissue sections was performed to detect ER expression in female patients with PTC (n = 89) and nodular thyroid goiter (NTG; n = 30) using the Elivision™ plus two-step system. The relationships between ER subtype expression and clinicopathological/biological factors were further analyzed.ResultsThe positive percentage and expression levels of ERα were significantly higher in female PTC patients of reproductive age (18–45 years old; n = 50) than age-matched female NTG patients (n = 30), while ERβ1 exhibited the opposite pattern. There was no difference in ERα or ERβ1 expression between female PTC patients of reproductive age and those of advanced reproductive age (>45 years old; n = 39). In the female PTC patients of reproductive age, ERα expression level was positively correlated with that of Ki-67, while ERβ1 was negatively correlated with mutant P53. Furthermore, more patients with exclusively nuclear ERα expression had extrathyroidal extension (ETE) as compared with those with extranuclear ERα localization. VEGF expression was significantly decreased in female PTC patients of reproductive age with only nuclear ERβ1 expression when compared with those with extranuclear ERβ1 localization. In PTC patients of advanced reproductive age, neither ERα nor ERβ1 expression showed any correlation with that of Ki-67, mutant P53, VEGF, tumor size, TNM stage, ETE, or lymph node metastases.ConclusionsThe differential expression patterns of the two ER subtypes between PTC and NTG indicate that ERα may be a useful immunohistochemical marker for differential diagnosis of PTC. The associations of ER subtype expression with Ki-67, mutant P53, VEGF expression and ETE in female PTC patients of reproductive age suggest that estrogen-activated ERα may mediate stimulatory effects on PTC growth and progression whereas ERβ1 has some inhibitory actions.

Administration of DHEA augments progesterone production in a woman with low ovarian reserve being transplanted with cryopreserved ovarian tissue

In recent years cryopreservation of ovarian tissue prior to potentially gonadotoxic treatment for malignant disease has proved to be an option for preservation of the reproductive function including fertility [1]. Following successful cancer treatment women have chosen to have transplantation of their frozen-thawed tissue if ovarian failure occurred as a consequence of cancer treatment. The autotransplanted tissue has in various centers resulted in the re-establishment of ovarian function leading to the return of fertility and the birth of healthy children [2, 3]. However, the ovarian reserve in the transplanted tissue typically is very low as currently only a limited number of follicles survive the entire procedure including freezing, thawing and transplantation [4]. This diminished reserve is reflected by persistent low levels of AMH [4], limiting the efficacy of controlled ovarian stimulation (COS) with exogenous FSH. In terms of fertility treatment, the women who have had frozen/thawed ovarian tissue transplanted often resemble poor responder patients and patients of advanced reproductive age. Attempts to augment the number of developing follicles by administration of oral DHEA for some months in the latter category of women have been reported [5–7], there being a growing literature describing a higher oocyte yield following COS and oocytes showing a better quality and thereby improving the reproductive outcome [5–7]. The particular mechanism by which DHEA may enhance follicle survival and growth has not yet been fully elucidated, but conversion of DHEA to androgens and an androgen priming effect on early stages of follicular development leading to an increased FSH receptor expression is one possible mechanism [8]. Although the vast majority of DHEA in the body is produced by the adrenals one obstacle in defining a more precise function of DHEA in improving follicle recruitment is the fact that the circulating DHEA is the sum of the local productions in the ovaries and those of adrenal glands [9]. In this study we observed the ovarian and endocrine events following DHEA administration in a woman, who had normal adrenal function but with very low ovarian reserve consequent to transplantation of frozen/thawed ovarian tissue, being postmenopausal at the time of transplantation. Only a fraction of frozen/thawed tissue from one ovary had been grafted with subsequent low ovarian reserve and evidenced by few follicles. This situation allowed a more direct evaluation of the endocrinological effect of DHEA administration on the synthesis of sex steroids.

Regulation of mitochondrial genome inheritance by autophagy and ubiquitin-proteasome system: implications for health, fitness, and fertility.

Mitochondria, the energy-generating organelles, play a role in numerous cellular functions including adenosine triphosphate (ATP) production, cellular homeostasis, and apoptosis. Maternal inheritance of mitochondria and mitochondrial DNA (mtDNA) is universally observed in humans and most animals. In general, high levels of mitochondrial heteroplasmy might contribute to a detrimental effect on fitness and disease resistance. Therefore, a disposal of the sperm-derived mitochondria inside fertilized oocytes assures normal preimplantation embryo development. Here we summarize the current research and knowledge concerning the role of autophagic pathway and ubiquitin-proteasome-dependent proteolysis in sperm mitophagy in mammals, including humans. Current data indicate that sperm mitophagy inside the fertilized oocyte could occur along multiple degradation routes converging on autophagic clearance of paternal mitochondria. The influence of assisted reproductive therapies (ART) such as intracytoplasmic sperm injection (ICSI), mitochondrial replacement (MR), and assisted fertilization of oocytes from patients of advanced reproductive age on mitochondrial function, inheritance, and fitness and for the development and health of ART babies will be of particular interest to clinical audiences. Altogether, the study of sperm mitophagy after fertilization has implications in the timing of evolution and developmental and reproductive biology and in human health, fitness, and management of mitochondrial disease.

The use of recombinant luteinizing hormone in patients undergoing assisted reproductive techniques with advanced reproductive age: a systematic review and meta-analysis

To evaluate the effect of recombinant LH in assisted reproduction technology (ART) cycles in patients of advanced reproductive age. A systematic review and meta-analysis. Published randomized controlled clinical trials comparing recombinant LH plus recombinant FSH versus recombinant FSH only in patients of advanced reproductive age. Patients 35 years and older undergoing assisted reproduction. Recombinant LH plus recombinant FSH controlled ovarian hyperstimulation (COH) versus recombinant FSH stimulation only in assisted reproduction cycles. Implantation and clinical pregnancy. Seven trials were identified that met inclusion criteria and comprised 902 assisted reproduction technology cycles. No differences in serum E(2) on the day of hCG administration were reported in any trials. Two trials reported lower oocyte yield and one trial reported lower metaphase II oocyte yield in the recombinant LH-supplemented group. One trial reported higher fertilization rates in the recombinant LH-supplemented group. In a fixed effect model, implantation was higher in the recombinant LH-supplemented group (odds ratio 1.36, 95% confidence interval 1.05-1.78). Similarly, clinical pregnancy was increased in the recombinant LH-supplemented group (odds ratio 1.37, 95% confidence interval 1.03-1.83). The addition of recombinant LH to ART cycles may improve implantation and clinical pregnancy in patients of advanced reproductive age.

The predictability of serum anti-Müllerian level in IVF/ICSI outcomes for patients of advanced reproductive age

BackgroundThe role of serum anti-Müllerian hormone (AMH) as predictor of in-vitro fertilization outcomes has been much debated. The aim of the present study is to investigate the practicability of combining serum AMH level with biological age as a simple screening method for counseling IVF candidates of advanced reproductive age with potential poor outcomes prior to treatment initiation.MethodsA total of 1,538 reference patients and 116 infertile patients aged greater than or equal to 40 years enrolled in IVF/ICSI cycles were recruited in this retrospective analysis. A reference chart of the age-related distribution of serum AMH level for Asian population was first created. IVF/ICSI patients aged greater than or equal to 40 years were then divided into three groups according to the low, middle and high tertiles the serum AMH tertiles derived from the reference population of matching age. The cycle outcomes were analyzed and compared among each individual group.ResultsFor reference subjects aged greater than or equal to 40 years, the serum AMH of the low, middle and high tertiles were equal or lesser than 0.48, 0.49-1.22 and equal or greater than 1.23 ng/mL respectively. IVF/ICSI patients aged greater than or equal to 40 years with AMH levels in the low tertile had the highest cycle cancellation rate (47.6%) with zero clinical pregnancy. The nadir AMH level that has achieved live birth was 0.56 ng/mL, which was equivalent to the 36.4th percentile of AMH level from the age-matched reference group. The optimum cut-off levels of AMH for the prediction of nonpregnancy and cycle cancellation were 1.05 and 0.68 ng/mL, respectively.ConclusionsTwo criteria: (1) age greater than or equal to 40 years and (2) serum AMH level in the lowest tertile (equal or lesser than 33.3rd percentile) of the matching age group, may be used as markers of futility for counseling IVF/ICSI candidates.

Alternative strategies to in vitro fertilization/intracytoplasmic sperm injection treatment for aged infertile women.

This study aimed to maximize the chance of pregnancy and provide an optimal protocol for infertile female patients of advanced reproductive age as an alternative to in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment. We retrospectively analyzed medical records of 432 infertile women aged ≥38 at the beginning of the treatment. Stepwise non-IVF/ICSI treatments using timed intercourse or intrauterine insemination, with or without controlled ovarian stimulation, were adopted for all patients. In this population, we extracted 8 representative infertility factors and examined these effects on fertility rate by calculating clinical pregnancy rate. The prognosis for infertile women possessing at least one of the three factors, 'advanced female age (≥42 years)', 'endometriosis/adenomyosis', and 'tubal infertility' was apparently poor because only 5 out of 155 women were able to conceive (1.02% per cycle). In contrast, 95 patients without the four factors, 'advanced female age', 'endometriosis/adenomyosis', 'tubal infertility', and 'male infertility', were more likely to conceive (9.14% per cycle). Fertility centers can offer appropriate protocols for non-IVF/ICSI treatment and establish guidelines for aged infertile patients by examining infertility factors and considering their combinations.

Evaluation of two doses of recombinant human luteinizing hormone supplementation in down-regulated women of advanced reproductive age undergoing follicular stimulation for IVF: a randomized clinical study

Objectives To evaluate the effects of mid-follicular recombinant human luteinizing hormone (rhLH) supplementation in down-regulated women of advanced reproductive age undergoing in vitro fertilization (IVF). Study design This was a prospective, randomized parallel-group study (allocation 1:1) including 187 normogonadotrophic infertile patients aged ≥35 years. Subcutaneous triptorelin was used for pituitary desensitization, and ovarian stimulation was achieved with recombinant human follicle-stimulating hormone (rhFSH) either alone (Group 1) or in combination with rhLH in one of two daily doses: 37.5 IU (Group 2) or 75 IU (Group 3). Ovarian stimulation characteristics and IVF outcome were evaluated. The main outcome was pregnancy rate. Results A total of 62, 62 and 63 patients were randomized to groups 1, 2 and 3 respectively, and 56, 54 and 55 patients respectively were available for final analysis of the results. Follicular development and oocyte yield were significantly higher in group 1 patients compared with patients in groups 2 and 3. Oocyte maturity and number of oocytes fertilized were also higher in group 1 patients; this difference almost reached statistical significance. No significant difference in implantation and clinical pregnancy rates was found among the three treatment groups. Conclusions rhLH supplementation is not a useful tool for patients of advanced reproductive age in ovarian stimulation protocols using an appropriate gonadotrophin-releasing hormone agonist and a step-down regimen of rhFSH.