Natural Cycle In Vitro Fertilization Research Articles

Review of minimally disruptive in vitro fertilization (IVF) approaches as a strategy for assisted human conception

As a type of assisted reproductive technology (ART), in vitro fertilization (IVF) has been available for more than 4 decades, with the first successful birth using conventional IVF (C-IVF) occurring in 1978. C-IVF has become increasingly available and accessible over the years and is currently a widely used alternative treatment option for prospective parents experiencing infertility. In addition, science and technological advancements have given rise to other IVF techniques that allow families to choose the ART that best fits their personal and unique needs. Among the other IVF techniques, natural cycle IVF, mild stimulation IVF, and in vitro maturation are notable for being less disruptive to the female body and are referred to as minimally disruptive ARTs (MDARTs). However, deciding which MDART to choose is a complex and daunting task that precedes an already emotionally, financially, and physically taxing process. This review explores these modern ART strategies, including protocols, advantages, and limitations, as well as provides the MDART decision matrix that translates these considerations into a practical decision-making guide for patients seeking IVF.

Nurturing Hope: Reproductive Outcomes with Sinosomatics following Unsuccessful in vitro Fertilization Attempts

Introduction: For women who have experienced failed attempts at in vitro fertilization (IVF) and face medical issues, leading to infertility, the renewed effort to seek fertility treatment, coupled with decreasing likelihood of success, can exert substantial emotional and physical strains. Consequently, many couples opt to discontinue treatment before attaining pregnancy. The objective of this study was to evaluate the reproductive outcomes in patients with unsuccessful prior IVF attempts who received a complementary treatment designed to alleviate emotional distress and burden. Patients and Methods: A retrospective analysis of data from infertile patients who initiated the complementary intervention at a private clinic between January 2014 and December 2016 was conducted. Information on diagnosis, history of infertility, prior assisted reproductive technology treatments, mode of conception, and pregnancy outcomes were retrieved. Results: The data of 133 patients with a history of one or more unsuccessful IVF treatments were analyzed. Patients had an average age of 36.7 years (±4.4 SD) and had been experiencing infertility for an average of 4.6 years (±2.7 SD). The two main causes of their infertility were endometriosis (36.1%, 48 patients) and diminished egg quality (31.6%, 42 patients). By May 2020, a significant proportion of the patients, 81.2% (108 patients), had achieved pregnancy, leading to 94 live births, which represents a 70.7% success rate. These pregnancies mostly resulted from natural cycle IVF (35.1%), donor cycles (23.4%), and conventional IVF (21.3%). The dropout rate was comparatively low at 23.3%. The median time from the start of complementary treatment to delivery was 18 months, with a range of 12–28 months. Conclusions: This study highlights the potential value of complementary treatment approaches in conjunction with standard medical care for women who have experienced unsuccessful IVF treatments in the past and thus face a reduced chance of motherhood. The reported 71% live birth rate is notably high, indicating that the inclusion of complementary treatments may provide women with past IVF failures a tangible opportunity for achieving successful pregnancy and childbirth. However, these findings need to be confirmed through randomized controlled studies.

Comparison of Pregnancy Outcomes Between Fresh Embryo Transfer in a Natural IVF Cycle and IUI Cycle Among Infertile Young Women

Background: The purpose of the current study was comparing pregnancy outcomes for natural cycle in vitro fertilization (IVF) per fresh embryo transfer (ET) and oocyte pick-up (OPU) in intrauterine insemination (IUI).
 Methods: This was a retrospective cohort study of women who underwent either IUI (n=246) or OPU with fresh ET for natural cycle IVF (n=291), conducted between April 2017 and February 2018 at the Center for Reproductive Medicine and Implantation Research, Sugiyama Clinic Shinjuku, Tokyo, Japan. Patients in both groups did not receive ovarian stimulation and luteal support; gonadotropin-releasing agonist spray was administered 35 hr before OPU or IUI. The clinical pregnancy rate was compared between the IUI and IVF groups. Data analysis was based on the number of cycles. The p≤0.05 was considered significant.
 Results: The clinical pregnancy rate per OPU in the IVF group was higher than the one in IUI group (20.6% vs. 10.1%), and the difference was significant (p<0.01). The pregnancy rate for natural cycle IVF calculated per fresh ET was 36.8%. The miscarriage rate did not significantly differ between the IVF (4.1%) and IUI (8.0%) groups.
 Conclusion: Fresh ET in natural cycle IVF provides a higher implantation rate than IUI.

Comparison of Pregnancy Outcomes Between Fresh Embryo Transfer in a Natural IVF Cycle and IUI Cycle Among Infertile Young Women

Background:The purpose of the current study was comparing pregnancy outcomes for natural cycle in vitro fertilization (IVF) per fresh embryo transfer (ET) and oocyte pick-up (OPU) in intrauterine insemination (IUI).Methods:This was a retrospective cohort study of women who underwent either IUI (n=246) or OPU with fresh ET for natural cycle IVF (n=291), conducted between April 2017 and February 2018 at the Center for Reproductive Medicine and Implantation Research, Sugiyama Clinic Shinjuku, Tokyo, Japan. Patients in both groups did not receive ovarian stimulation and luteal support; gonadotropin-releasing agonist spray was administered 35 hr before OPU or IUI. The clinical pregnancy rate was compared between the IUI and IVF groups. Data analysis was based on the number of cycles. The p≦0.05 was considered significant.Results:The clinical pregnancy rate per OPU in the IVF group was higher than the one in IUI group (20.6% vs. 10.1%), and the difference was significant (p<0.01). The pregnancy rate for natural cycle IVF calculated per fresh ET was 36.8%. The miscarriage rate did not significantly differ between the IVF (4.1%) and IUI (8.0%) groups.Conclusion:Fresh ET in natural cycle IVF provides a higher implantation rate than IUI.

P–768 Childhood growth of singletons conceived following in vitro fertilization (IVF) - does gonadotropin-stimulation matter?

Abstract Study question Is there a difference in growth or weight gain of children conceived after IVF with or without gonadotropin-stimulation compared to standard growth references? Summary answer: We observed no difference in growth between children conceived after IVF with or without gonadotropin-stimulation and spontaneously conceived children. What is known already In recent studies, singletons conceived after IVF cycles had lower birth weight than spontaneously conceived singletons. The etiology of the impaired intrauterine growth is unclear, but insufficiency of placental function or possible epigenetic effects is discussed. Data regarding normalization or continuation of reduced birth weight are controversial. The growth of children born after unstimulated natural cycle IVF (NC-IVF) has never been studied. Study design, size, duration Single-center, university based cohort study. 139 singletons born after NC- IVF and children born after conventional gonadotropin stimulated IVF (cIVF) in 2010 –2017 were studied. Stimulation dosage in cIVF was ≥150 IU/d human gonadotropin. Participants/materials, setting, methods We collected weight, length and head circumference at birth and at one, two, four, six, 12, 18 and 24 months. We calculated standard deviation scores based on national growth references. Growth parameters (weight, length and head circumference) were compared between NC-IVF and cIVF singletons (stimulated with ≥150 IU/d human gonadotropin) using Mann-Whitney U tests. Main results and the role of chance In general, growth of children conceived after IVF did not differ from national references. Of the 139 singletons conceived, 98 singletons were conceived after NC-IVF and 41 after cIVF. The parents did not differ in ethnicity, age, BMI or health status between groups, and there was no significant difference in gestational age, pregnancy complications and smoking or breastfeeding habits either. The median birth weight in NC-IVF children was 3.4kg (0.1 standard deviation score, SDS) and in cIVF 3.3kg (–0.3 SDS) (p = 0.53). Median length at birth in NC-IVF was 50cm (–0.5 SDS) and did not differ from cIVF children 50cm (–0.8 SDS) (p = 0.52). At age 12 months, the median weight was 9.3kg (0.0 SDS) for NC-IVF children compared to 9.0kg (–1.7 SDS) for cIVF children (p = 0.44). Median lengths was 75cm (0.1 SDS) in NC-IVF versus 71cm (–1.6 SDS) in cIVF children (p = 0.89). At age 24 months, median weight in NC-IVF children was 12.3 kg (0.3 SDS) versus 10.5 kg (–1.2 SDS) in cIVF (p = 0.72) and median lengths 87.5cm (0.1 SDS) in NC-IVF versus 87.6 cm (0.1 SDS) in cIVF children. These discrete non-significant differences in weight and length gain compared to standardized growth curves and between the two groups are reassuring. Limitations, reasons for caution Willingness to participate is prone to selection bias. Further studies with larger samples are needed to confirm these findings. Wider implications of the findings: This is the first study investigating weight and length gain in children after unstimulated IVF. Growth is an important proxy for the health of children. These reassuring results are of imminent importance for the children born after IVF and their parents. Trial registration number BASEC (ID 2015–00235)

Natural-cycle in vitro fertilization (IVF) combined with in vitro maturation in infertile patients with polycystic ovarian syndrome (PCOS) requiring IVF

ObjectiveIn this study, we report an experience of 59 natural-cycle IVF combined with in vitro oocyte maturation (IVF/M) cycles in patients with PCOS requiring IVF recruited based on limitations to afford a conventional IVF treatment in a 9-years period. Results of IVF/M were compared with 164 cycles of IVF in PCOS patients. Material and methodsIn IVF/M cycles only hCG priming was used before oocyte recovery, with in vitro maturation of immature oocytes in a commercial medium. In conventional IVF group, recombinant FSH (rFSH) and GnRH agonist/antagonist for ovarian stimulation were used. In both groups, fertilization was achieved by intracytoplasmic sperm injection (ICSI) of mature oocytes and fresh embryos transferred at day 2 or day 3. ResultsIn all IVF/M cycles oocytes and transferable quality embryos were obtained, only in 6 IVF/M cycles mature oocytes were obtained at oocyte capture day. Clinical pregnancy rate per cycle was 39.0% vs 53.6% (p = 0.0682) and delivery rate per cycle was 30.5% vs 42.6% (p = 0.1209) in IVF/M and conventional IVF respectively. Patients with ovarian hyperstimulation syndrome (OHSS) were 0% in IVF/M vs 6.7% in conventional IVF (p = 0.0399). ConclusionOur experience in a private clinic in Mexico suggests that IVF/M can be a useful initial strategy to treat PCOS patients requiring IVF with comparable delivery rates to conventional IVF and a decreased risk of ovary hyperstimulation. IVF/M may be indicated to patients with limited resources paying without insurance for their infertility treatment.

IVF procedures are not, but subfertility is associated with neurological condition of 9-year-old offspring

In vitro fertilization (IVF) is not associated with neurological abnormalities in offspring's early childhood. Yet, it is unclear whether this is also true for school age. Neither do we know the role of parental subfertility in offspring's neurological development. The present study examined neurological condition at 9 years of 57 singletons born after controlled ovarian hyperstimulation IVF (COH-IVF), 46 singletons born after modified natural cycle IVF (MNC-IVF) and 66 singletons born to subfertile parents after natural conception (Sub-NC). To assess the effect of subfertility, the groups were pooled to form a subfertile group, and compared with a prospectively followed fertile reference group (n = 282). The sensitive Minor Neurological Dysfunction (MND) examination was used, resulting in the detailed Neurological Optimality Score (NOS) and the prevalence of the clinically relevant complex MND. Neurological condition of the three subfertile groups did not differ significantly: median NOS was 53 in each subfertile group and the prevalence of complex MND in the three subfertile groups was 30%, 37% and 36%, respectively. However, the NOS was lower and the prevalence of complex MND higher in children born to subfertile couples than in children of fertile couples (adjusted mean difference [95% CI]: −4.48 [−5.53 to −3.42]) and adjusted OR [95% CI]: 5.13 [2.60–10.16], respectively). We conclude that ovarian hyperstimulation, in vitro procedures, and the combination of both were not associated with a less favourable neurological outcome of 9-year-old singletons. However, the presence of parental subfertility was associated with less favourable neurological outcome of offspring at 9 years follow up.

Why more is less and less is more when it comes to ovarian stimulation

The purpose of the present study is to describe the possible mechanisms which may explain the apparent paradox of "less is more." Mild ovarian stimulation for in vitro fertilization (IVF) minimizes ovarian hyperstimulation syndrome (OHSS) and multiple gestations without compromising the pregnancy rate (PR). The pertinent English literature (PubMed) addressing mild stimulation for IVF/assisted reproductive technology (ART) and publications addressing "mild" or "soft" controlled ovarian stimulation (COS) vs conventional COS for IVF, OHSS, natural cycle IVF, and IVF outcome in association with COS was searched. Four possible mechanisms can be put forward to explain the apparent paradox of "less is more." (1) In the natural or mild stimulation cycles, the healthiest follicles are selected by the principle of "quality for quantity"; (2) high estradiol (E2) in the late follicular phase significantly correlated with higher rates of small for gestational age (SGA) and low-birth-weight (LBW) neonates; (3) anti-Mullerian hormone (AMH), LH, testosterone, and E(2) are significantly higher in natural cycle (NC)-IVF than in stimulated IVF follicles, suggesting an alteration of the follicular metabolism in stimulated cycles; and (4) supraphysiological E(2) may increase the growth hormone-binding protein (GH-BP) bio-neutralizing GH and diminishing the resultant insulin-like growth factor (IGF) levels, necessary for optimal synergism with follicle-stimulating hormone (FSH). It is suggested to aim at the retrieval of around eight to ten eggs. Mild stimulation should be the common practice for IVF. In cases where more than ten ova are retrieved or high E(2) levels are reached, either intentionally or unintentionally, "freeze-all policy" should be considered and embryo transfer (ET) done in a subsequent natural cycle.

Gonadotropin dose is negatively correlated with live birth rate: analysis of more than 650,000 assisted reproductive technology cycles

To evaluate the correlation between total gonadotropin dose and live birth rate. Retrospective analysis. Not applicable. A total of 658,519 fresh autologous cycles of in vitro fertilization (IVF) reported to the Society for Assisted Reproductive Technology from 2004 to 2012. None. Logistic regression models were fitted to live birth rates with the use of categorized values for total FSH dose and number of oocytes retrieved as the primary predictor variables. To reduce the effect of the most significant confounders that may lead physicians to prescribe higher doses of FSH, additional analyses were performed limited to good-prognosis patients (<35 years of age, body mass index <30 kg/m(2), and no diagnosis of diminished ovarian reserve, endometriosis, or ovulatory disorder) and including duration of gonadotropin treatment. Live birth rate significantly decreased with increasing FSH dose, regardless of the number of oocytes retrieved. The statistically significant decrease in live birth rate with increasing FSH dose remained in patients with good prognosis, and regardless of female age, except for women aged ≥ 35 years with 1-5 oocytes retrieved. This analysis suggests that physicians may wish to avoid prescribing a high dose of FSH. However, the results of this study do not justify the use of minimal-stimulation or natural-cycle IVF.

Increased time to pregnancy is associated with less optimal neurological condition in 4-year-old singletons, in vitro fertilization itself is not.

Does ovarian hyperstimulation, the in vitro procedures required for in vitro fertilization (IVF)/ intracytoplasmic sperm injection or the combination of both, affect the neurological outcome of 4-year-old singletons? Ovarian hyperstimulation, the in vitro procedure and the combination of both, were not associated with the worse neurological outcome in 4-year-old singletons. Assisted reproduction techniques (ARTs) are not associated with neurological dysfunction during the first post-natal years; however, effects on the long-term neurological outcome are still inconclusive. An increased time to pregnancy (TTP, a proxy for the severity of subfertility) has been associated with a less optimal neurological condition at age 2. The present study focuses on the neurodevelopmental outcome of 4-year-old ART-offspring. Longitudinal, prospective follow-up study. Four-year-old singletons born to subfertile parents (subfertile group, n = 195), including singletons born after controlled ovarian hyperstimulation IVF (COH-IVF, n = 63), modified natural cycle IVF (MNC-IVF, n = 53) and natural conception (Sub-NC, n = 79). Data on underlying cause of subfertility and TTP were present. In addition, we assessed newly recruited 4-year-old singletons born to fertile parents after natural conception (reference group, n = 98). Neurological development was evaluated with the neurological examination according to Hempel, resulting in a neurological optimality score (NOS), a fluency score and the occurrence of the clinically relevant form of minor neurological dysfunction (complex MND). The primary outcome was the fluency score, as fluency of movements is easily reduced by subtle brain dysfunction. Data were analysed with univariable and multivariable regression analyses, in which special attention was paid to sex differences in the neurological outcome. The fluency score, NOS and the prevalence of complex MND were similar in COH-IVF, MNC-IVF and Sub-NC children. The neurological condition of children born to subfertile parents was similar to that of children of fertile parents and was independent of the underlying cause of subfertility. No statistically significant associations were found between TTP and the fluency score and NOS. However, a positive correlation was found between TTP and the prevalence of complex MND (TTP in years, adjusted odds ratio [OR] [95% confidence interval, CI]: 1.207 [1.038 to 1.404], P = 0.014); a correlation which could be attributed to girls, in whom an evident positive correlation was present (adjusted OR [95% CI]: 1.542 [1.161 to 2.047], P = 0.003). A similar association was absent in boys. The prospective design of our study and small post-natal attrition rate (9.3%) reduced potential selection bias based on the child's development or health. The assessors were blind to the mode of conception, except for the group of children born to fertile parents, which was newly recruited. The study lacks sufficient power to conclude firmly that increased TTP is associated with a higher prevalence of complex MND. Our study suggests that the severity of subfertility, rather than its simple presence or components of IVF treatment, affects the neurological outcome. Moreover, girls may be neurologically more vulnerable for the effect of severity of subfertility. The finding that the severity of subfertility may be the decisive factor rather than the presence of a history of subfertility per se corroborates previous reports. Our results cannot be generalized to multiples, as we studied singletons only. The study was financially supported by the University Medical Center Groningen, grant number: 754510, the Junior Scientific Masterclass, the Postgraduate School Behavioural and Cognitive Neurosciences and the Cornelia Foundation, Groningen, The Netherlands. The authors have no conflicts of interest to declare.

Follicular-phase ovarian follicular fluid and plasma cytokine profiling of natural cycle in vitro fertilization patients

To characterize follicular fluid (FF) and systemic cytokine profiles at various time points during the natural-cycle follicular and periovulatory phases. Observational clinical study across two consecutive cycles. Hospital-basedin vitro fertilization program. Ten women undergoing modified natural-cycle invitro fertilization (MNC-IVF). Plasma and follicular fluid (FF) collection. Forty FF cytokine concentrations from individual follicles and plasma from each patient were determined by fluid-phase multiplex immunoassay in two consecutive cycles: 1) tracking cycle-midfollicular or luteal surge; and 2) treatment cycle-periovulatory (at the time of MNC-IVF). Demographic, cycle, and cytokine data were compared with the use of chi-square, paired-scores t test, or Wilcoxon signed ranks tests. Fluctuations in various FF cytokines were evident during the follicular phase: Levels of interleukin (IL) 6 and IL-8 were higher in periovulatory samples, and IL-1 receptor antagonist and vascular endothelial growth factor were elevated earlier in the cycle. Luteal surge profiles were similar to those found in periovulatory samples. Conversely, circulatory cytokine concentrations were more stable during the follicular phase. These findings present an extensive physiologic reference profile of FF cytokines associated with antral folliculogenesis and highlight the compartmentalization of systemic and intraovarian cytokine networks in natural cycles.

Natural cycle in vitro fertilization implantation rates compared to stimulated in vitro fertilization and role of serum antimullerian hormone levels

Objective: The objective of this study is to compare implantation and singleton live birth rates between natural cycle in vitro fertilization (NCIVF) and stimulated IVF. Stratify the results by age and antimullerian hormone (AMH). Design: Retrospective cohort trial of patients who underwent unstimulated IVF between 2007 and 2011. Stimulated patient data from the 2010 Centers for Disease Control (CDC) report. Setting: Private practice. Patients: Infertility patients < 43-year-old. Intervention: None. Main Outcome Measures: (1) Implantation rates stratified by age and AMH (2) singleton pregnancy rates. Results: A total of 1288 cycles of NCIVF were compared to 94,976 cycles from CDC. In patients <35 years the implantation rates for NCIVF and stimulated IVF were 35.1% versus 36.9%. In patients 35-37, 38-40 and 41-42 years old, the NCIVF and stimulated IVF implantation rates were 33.9% versus 27.0%, 30.4% versus 17.7%, and 21.4% versus 9.6%. NCIVF implantation rates were independent of AMH at all ages and all levels of AMH. The singleton live birth rates per embryo transfer for both NCIVF and the CDC reported stimulated IVF were similar for all age groups. Conclusions: Implantation rates were superior in patients 35-40 undergoing NCIVF compared with stimulated IVF. In NCIVF implantation rate was independent of AMH. The live singleton birth rates per embryo transfer for NCIVF and stimulated IVF are similar.

Delivery following natural cycle in vitro fertilization in a patient with endometriosis-associated hemorrhagic ascites

Hemorrhagic ascites represents an unusual presentation of endometriosis and has been described in only 63 women since 1954. Treatment options for patients suffering from infertility associated with hemorrhagic ascites may be limited, as the use of fertility medications has been demonstrated to exacerbate ascites. We report successful treatment with term delivery of a healthy infant in a 29-year-old nulligravid patient with laparoscopically confirmed endometriosis-associated hemorrhagic ascites using natural cycle in vitro fertilization (NCIVF). NCIVF may be successfully utilized in treating patients diagnosed with unusual fertility problems, such as endometriosis-associated hemorrhagic ascites, in which the use of gonadotropins may be contraindicated.

Impact of exogenous gonadotropin stimulation on circulatory and follicular fluid cytokine profiles.

Background. The natural cycle is the prototype to which we aspire to emulate in assisted reproduction techniques. Increasing evidence is emerging that controlled ovarian hyperstimulation (COH) with exogenous gonadotropins may be detrimental to oogenesis, embryo quality, and endometrial receptivity. This research aimed at assessing the impact of COH on the intrafollicular milieu by comparing follicular fluid (FF) cytokine profiles during stimulated in vitro fertilization (IVF) and modified natural cycle (MNC) IVF. Methods. Ten women undergoing COH IVF and 10 matched women undergoing MNC IVF were recruited for this pilot study. 40 FF cytokine concentrations from individual follicles and plasma were measured by fluid-phase multiplex immunoassay. Demographic/cycle/cytokine data were compared and correlations between cytokines were computed. Results. No significant differences were found between COH and MNC groups for patient and cycle demographics, including outcome. Overall mean FF cytokine levels were higher in the MNC group for 29/40 cytokines, significantly so for leukaemia inhibitory factor and stromal cell-derived factor-1α. Furthermore, FF MNC cytokine correlations were significantly stronger than for COH data. Conclusions. These findings suggest that COH perturbs intrafollicular cytokine networks, in terms of both cytokine levels and their interrelationships. This may impact oocyte maturation/fertilization and embryo developmental competence.

Kinderwunsch der Frau ab 40 Jahren

Spontaneous conceptionInfertility treatment for women over 40 years of age has a limited chance of success. The rapidly decreasing fertility requires a treatment with the highest chance of pregnancy per treatment time. If a woman has been trying to become pregnant for less than 0.5–1 year and if infertility factors such as tubal blockage or low sperm count have been excluded, spontaneous conception should be envisaged.Intrauterine insemination and In vitro fertilizationIntrauterine insemination (IUI) should only be performed if an andrological infertility factor has definitely been diagnosed and should be limited to only a few treatment cycles and to a maximum female age of approximately 42 years. Conventional in vitro fertilization (IVF) should be preferred over a natural cycle IVF in cases where there is a high ovarian reserve. A natural cycle IVF can be considered in expectation of a poor response. A conventional IVF should only be performed if the expected chance of fertilization per stimulation cycle is at least 5 %. In this case the female age limit for a conventional IVF is around 43–44 years.

Cumulative pregnancy rates after minimal ovarian stimulation for in vitro fertilization

In recent years there has been an increasing interest in minimal ovarian stimulation (MOS)protocols. Outcomes of in vitro fertilization (IVF) treatment often represent pregnancy rates per IVF cycle. But MOS cycles have a lower pregnancy rates per IVF cycle reported. Our aim of this study is to determine the viability of MOS protocols by looking at the cumulative pregnancy rates. Retrospective cohort study. We estimated cumulative pregnancy rates among infertile patients undergoing a clomiphene citrate based MOS or natural cycle IVF protocols between 2009 and 2012 in one private infertility centre. A total of 1700 patients who started their treatment in 2009 were enrolled in this study. Survival curves and Kaplan Meier methods to analyze clinical pregnancy rates (CPRs) stratified patients by their age(≤29,30-32,33-35,36-38,39-41,42-44,45≤) at the start of the treatment in a retrospective cohort with respect to the number of oocyte retrieval (OR) cycles. Among patients who were younger than 38 years of age, the corresponding pregnancy rates increase radically to 86.6% between cycle 1 and 5, increasing moderately to 96.4% between cycles 6 and 10. Among patients who were 39-41 years of age, the corresponding pregnancy rates increased moderately to 687% between cycles 1 and 10. Among patients who were over 42-44 years of age, the corresponding pregnancy rates also increased moderately to 45.1% between cycles 1 and 15. The cumulative pregnancy rates decreased with increasing age, and age stratified curves (≤38 vs. 39≤ years) were significantly different from one another (P<0.001). To our knowledge, this is the first report regarding cumulative pregnancy rates of only the MOS or natural cycle protocols. The results of our study demonstrate that it yields acceptable cumulative pregnancy rates in fertile patients up until their mid forties.

Overnight maturation of a metaphase I oocyte retrieved from a natural cycle using human tubular fluid: a case report

Since the first successful pregnancy and live birth was achieved through natural cycle in vitro fertilization (IVF) in 1978 [1], there have been many technological advancements and refinements of protocols and techniques through the years [2]. Ovarian hyperstimulation was favored over unstimulated cycles, due to the increased number of embryos available for transfer and hence increased success rate. However, stimulated IVF is also associated with side effects such as ovarian hyperstimulation syndrome [3] and it is costly [4]. For patients who have failed to conceive after repeated stimulated IVF cycles, natural cycle IVF may be a cost-saving alternative [5, 6] which allows patients to avoid further exposure to the side effects associated with stimulated IVF cycles [7, 8]. However, one of the drawbacks of pure natural cycle IVF is its higher cancellations rates (28.9 % per cycle) and lower pregnancy rate (0 to 12.5 % per cycle) [5]. The main reasons for cancellation are premature ovulation before oocyte retrieval, failure to retrieve oocytes and retrieval of immature oocytes. The stage of maturation of the oocyte cannot be determined before retrieval as well. When an immature oocyte is retrieved, it is usually discarded and the cycle is cancelled. To maximize the utilization of the immature oocytes collected from unstimulated cycles, our centre evaluated our protocol and started incubating the immature oocytes overnight in human tubular fluid (HTF) (Irvine Scientific, USA) instead of discarding them. Standard IVF culture media has been shown to be as efficacious as specialized IVM media in ‘rescuing’ immature oocytes retrieved from standard stimulated IVF cycles [9]. When fully matured, the oocytes are fertilized, allowed to develop into embryos in culture and eventually transferred. We report the first case of a successful implantation and pregnancy achieved from this ‘rescue’ protocol in a natural IVF cycle.

Evidence-Based Management of Infertile Couples with Repeated Implantation Failure Following IVF

Embryo implantation depends on both embryo quality and the endometrial environment. Implantation failure has a complex, variable pathophysiology and is detrimental to the outcome of in vitro fertilization (IVF). Thus, patients with multiple implantation failure require an individualized approach to diagnosing and managing treatment options for future IVF cycles. These options should be based on concrete, unambiguous, consistent scientific evidence with random- ized, controlled trials. We review and discuss 14 treatment options: (i) blastocyst transfer, (ii) assisted hatching, (iii) co-culture, (iv) preimplanta- tion genetic screening, (v) hysteroscopy, (vi) sildenafil, (vii) salpingectomy for tubal disease, (viii) oocyte donation, (ix) transfer of six or more embryos, (x), intratubal embryo transfer, (xi) natural cycle IVF, (xii) antiphospholipid antibodies (APA) testing and treatment, (xiii) allogenic lymphocyte therapy, and (xiv) IV immunoglobin therapy. The approaches were evaluated based on available information from studies, expert opinions, consensus, etc. We conclude that blastocyst transfer, assisted hatching, salpingectomy for tubal disease, and hysteroscopy in IVF procedures are clinically effective. This review serves as a summary of current treatment options for clinicians to counsel patients and manage their expectations based on strong and reliable evidence.

Clinical outcomes for various causes of infertility with natural-cycle in vitro fertilization combined with in vitro maturation of immature oocytes

The clinical outcomes of different infertility causes (tubal factor, male factor, unexplained infertility, combination of tubal and male factors, and other/mixed factors) with natural-cycle in vitro fertilization/maturation (IVF/M) treatment were evaluated. There were no significant differences in the rates of IVM, IVF, and cleavage as well as the clinical pregnancy (30.4%-46.9%) and live birth rates among the five subgroups, which suggests that natural-cycle IVF/M is a suitable treatment for infertility of various causes with acceptable pregnancy and live birth rates.

Natural-cycle in vitro fertilization in poor responder patients: a survey of 500 consecutive cycles

To determine the role of the natural cycle for in vitro fertilization (IVF) in poor responder patients. Retrospective survey. Private center for assisted reproduction. 294 women who were poor responders in a previous IVF cycle. Analysis of 500 consecutive natural cycles IVF. Number of cycles with oocytes, pregnancy rate per cycle, per transfer, and implantation rate. Oocytes were found in 391 cases (78.1%), and cleaving embryos suitable for transfer were obtained in 285 cycles (57.0%). Pregnancy was observed in 49 cases, with a pregnancy rate of 9.8% per cycle, 17.1% per transfer, and 16.7% per patient. The patients were subdivided arbitrarily by the women's age into three groups. Patients 35 years old or younger showed a pregnancy rate of 18.1% per cycle, 29.2% per transfer, and 31.7% per patient. Women aged between 36 and 39 years showed a pregnancy rate of 11.7% per cycle, 20.6% per transfer, and 20.3% per patient. Women 40 years old or older showed a pregnancy rate of 5.8% per cycle, 10.5% per transfer, and 9.7% per patient. No differences were found for any of the evaluated parameters, independent of which cycle was the first, the second, third, fourth, or fifth, or further consecutive cycle. In poor responder patients, natural-cycle IVF is an effective treatment, especially in younger women.