Effects of anti-Müllerian hormone and follicle stimulating hormone levels on in vitro fertilization pregnancy rate

ObjectivesTo analyze the relationship between in vitro fertilization (IVF) pregnancy rate and basal serum hormone levels before patients begin an IVF course.Materials and methodsIn this retrospective study, we analyzed patients with anti-Müllerian hormone (AMH) data and IVF data from January 2009 to October 2012. Pregnancy rates were calculated by AMH and follicle stimulating hormone quartiles and analyzed using the independent samples t test. Furthermore, patients were divided into three groups by age. The Chi-square test was used to assess the association between the parameters and IVF pregnancy rates.ResultsFrom the 910 IVF treatment courses, 377 (41.4%) clinical pregnancies resulted. The pregnant and nonpregnant groups differed significantly in age and FSH and AMH levels. The pregnancy rate was 53.3% for patients aged <32 years and 22.1% for patients aged >38 years. The pregnancy rate was 53.4% for patients with FSH levels <5.6 mIU/mL and 25.8% for patients with FSH levels >8.9 mIU/mL. The pregnancy rate was 56.8% for patients with AMH levels >4.0 ng/mL and 20.0% for patients with AMH levels <1.1 ng/mL. Furthermore, among patients aged <40 years, AMH and FSH were significantly associated with pregnancy rate. Higher pregnancy rates were found among the groups with higher AMH levels than in groups with lower AMH levels.ConclusionFor patients aged <40 years, basal serum AMH level and FSH level affected the IVF pregnancy rate, and patients with higher AMH levels had better pregnancy rates.     

Does supplementation with recombinant luteinizing hormone prevent ovarian hyperstimulation syndrome in down regulated patients undergoing recombinant follicle stimulating hormone multiple follicular stimulation for IVF/ET and reduces cancellation rate for high risk of hyperstimulation?

Aim of this study was to assess the efficacy of recombinant luteinizing hormone (rLH) supplementation in late follicular phase in multiple follicular stimulation with recombinant follicle stimulating hormone (rFSH) in Triptoreline down-regulated patients undergoing IVF, on preventing clinical OHSS and cycles cancellation for OHSS risk. Nine hundred ninety-nine patients aged ≤40 with basal FSH ≤12 mUI/Ml were down-regulated before starting rFSH stimulation for oocytes recovery. Patients were allocated in two groups: (A) (501 patients) treated with 150 IU of rFSH eventually adjusting rFSH dosage day 7 of stimulation until recombinant human chorionic gonadotropin (rhCG) administration, (B) (498 patients) treated with 150 IU of rFSH and 75 IU of rLH since day 7 of stimulation until rhCG administration and adjusting rFSH at the same day. E2 the day of rhCG was higher in group B (p?<?0.0001); number of cycles cancelled in group A (42/8.3%) for risk of ovarian hyperstimulation syndrome (OHSS) was higher than group B (12/2.4%) (p?<?0.000001). We observed an increase in pregnancies in group B compared with group A (16.8% vs 11.9%) (p?<?0.05) and we observed also a larger number of clinical OHSS in group A than in group B (p?<?0.05).     

Serum Anti-müllerian hormone, follicle stimulating hormone and antral follicle count measurement cannot predict pregnancy rates in IVF/ICSI cycles

Purpose

To investigate whether serum anti-müllerian hormone (AMH), follicle stimulating hormone (FSH), or antral follicle count (AFC) are predictive for clinical pregnancy in in vitro fertilization (IVF) patients.

Methods

Serum AMH, inhibin B, FSH, luteinizing hormone (LH), estradiol (E2), prolactin, and thyroid stimulating hormone (TSH) levels and AFC of 189 women under 40 years of age were investigated. Pregnant and non-pregnant women were compared.

Results

Forty-seven (24.8 %) clinical pregnancies were observed in 189 women. There was no significant difference in terms of mean age, duration of infertility, body mass index, AMH, LH, FSH, E2, TSH, Inhibin B, AFC and total oocyte number between women who did and who did not become pregnant. Additionally, there was no significant difference in clinical pregnancy rates between the quartiles of AMH, FSH and AFC. (P values were 0.668, 0.071, and 0.252, respectively.)

Conclusion

Serum AMH and FSH, and AFC cannot predict clinical pregnancy in IVF patients under 40; the pregnancy rate tends to increase as AMH increases, although this remains non-significant.     

Anti-Müllerian hormone versus antral follicle count for defining the starting dose of FSH

This pilot study compared the efficacy and safety of two simple dosing algorithms, one based on anti-Müllerian Hormone (AMH) and the other on the antral follicle count (AFC), to determine the starting dose of recombinant FSH (rFSH) for ovarian stimulation in 348 women. Patients were randomized to a predefined AMH- or AFC-based algorithm. The proportion of cycles with the desired response was similar when rFSH dose was determined using AMH or AFC (35.2% versus 28.4%). There was a significant difference between the groups in the proportion of cycles with a hyperresponse (8.6% and 17.4%, but the incidence of ovarian hyperstimulation syndrome was similar (1.1% and 4.6%). There were no significant differences between two groups in outcomes, including implantation (19.3% versus 19.0%), clinical pregnancy (38.0% versus 46.9%), multiple pregnancy (16.5% versus 15.2%) and miscarriage (7.0% versus 8.3%). However, statistically significant differences in ovarian response were evident among the AMH and AFC subgroups: for AMH, Desired and Hypo; for AFC, Hypo and Hyper. This pilot study provides information for developing protocols to further validate the use of either AMH or AFC to guide the starting dose of rFSH in ovarian stimulation.The ideal outcome for couples undergoing IVF treatment is the birth of a healthy baby. One factor that might influence this is retrieving an adequate number of eggs, which are obtained using various treatment protocols. A group of drugs called gonadotrophins have been used for more than 20 years to stimulate the ovaries to produce eggs. However, the dose to start treatment has not been clearly defined. A few studies have looked at ways to use the best gonadotrophin dose for each woman, but to be useful in the clinic any approach needs to be simple and easy to use. This study compared the effectiveness and safety of two simple approaches to determining the starting dose of recombinant FSH (rFSH) for ovarian stimulation in women undergoing IVF. One was based on the concentration of a hormone secreted by developing eggs (anti-Müllerian hormone; AMH) and the other on the number of developing follicles (antral follicle count; AFC). The number of cycles achieving the desired response in terms of number of eggs was similar when rFSH dose was guided using AMH or AFC, and the incidence of ovarian hyperstimulation syndrome was also similar. In addition, rates of clinical pregnancy, multiple pregnancy and miscarriage did not differ between the two groups. However, patients with low AMH concentrations or low AFC had a poor response to ovarian stimulation. This pilot study provides useful information from which new studies can further assess these approaches to personalizing treatment during IVF.     

How to improve IVF results from a clinical point of view?

This study reports the last data of the literature on the possibilities of optimizing chances of pregnancy during in vitro fertilization attempts, our research concerning only the clinical point of view while excluding biologic possibilities. The selection of the patients, the management of controlled ovarian hyperstimulation protocols, the optimalisation of the transfer and the luteal phase support will be cross-reviewed.     

Cesarean versus vaginal delivery: whose risks? Whose benefits?

We reviewed the risks and benefits of vaginal and cesarean delivery to help frame the inherent trade-offs that should be considered as part of the informed consent discussion between patients and providers. We performed a targeted literature review for common complications of childbirth. Approximately 30% of women will experience a maternal or neonatal complication during childbirth. Both cesarean and vaginal delivery is associated with well-known measurable short- and long-term maternal and neonatal complications and benefits. Childbirth is not risk free. There are data available that can guide the informed consent process with objective quantifiable data that patients and providers can use to weigh risks and benefits of delivery methods.     

Effect of urinary versus recombinant FSH on clinical outcomes after frozen–thawed embryo transfers: a systematic review

Recent randomized trials, systematic reviews and cost-effectiveness analyses have demonstrated the relative efficacy, and in some cases superiority, of urinary gonadotrophins (uFSH, human menopausal gonadotrophin) compared with recombinant FSH (rFSH). However, the effectiveness of frozen-embryo transfers (FET) following ovarian stimulation with uFSH versus rFSH in the fresh cycle has not been well investigated. The objective of this study was to determine whether there are differences in clinical outcomes in women undergoing FET according to the type of gonadotrophin used during ovarian stimulation. Following a meticulous search, all published comparative studies of FET using ovarian stimulation were reviewed. Data on clinical outcomes were extracted and systematically presented. Using the agonist long protocol for down-regulation, five trials provided extractable data for live-birth and ongoing pregnancy rates following FET, as well as the cumulative live-birth, ongoing pregnancy and clinical pregnancy rates following fresh-embryo transfer and FET from the same cycle. There was no evidence of significant effect difference between the uses of uFSH versus rFSH regarding any of the outcomes. In conclusion there is insufficient evidence to determine whether the use of a certain type of gonadotrophin during ovarian stimulation affects the clinical outcomes in subsequent FET.Clinical efficiency in IVF procedures has been debated for years. Defining a unified goal, or endpoint, for IVF treatments has shown marked discrepancies among clinicians, regulatory bodies and organizations; with some regarding a clinical pregnancy, an ongoing pregnancy, a live-birth, or even a take-home baby as the primary outcome of IVF treatments. The objective of this systematic review was to determine the effectiveness of the use of urinary versus recombinant FSH on the results of frozen embryo transfers and the effect that this would have on the cumulative clinical results of IVF. This systematic review has shown that there is insufficient evidence to determine whether the use of a certain type of gonadotrophin during ovarian stimulation affects the clinical outcomes in subsequent frozen embryo transfers, such as live-birth rate, ongoing pregnancy rate, clinical pregnancy rate. With respect to cumulative rates, it is noted that no significant differences in live birth rate, ongoing pregnancy rate, and clinical pregnancy rate following fresh and frozen transfer cycles. It is concluded that well-designed and powered studies are needed to determine possible effects of the use of a certain type of gonadotrophin during ovarian stimulation on the clinical outcomes in subsequent frozen thawed embryo transfers.     

HMG versus recombinant FSH plus recombinant LH in ovarian stimulation for IVF: does the source of LH preparation matter?

Studies on the role of LH supplementation in patients undergoing assisted reproductive technique use different sources of LH bioactivity-containing preparations, daily doses and modes of administration. This review aims to critically present the available evidence comparing the effect of the two commercially available LH preparations (human menopausal gonadotrophin [HMG] and recombinant FSH + recombinant LH) with different sources of intrinsic LH bioactivity (HCG versus LH, respectively) on ovarian stimulation characteristics and IVF cycle outcomes. A literature review was conducted for all relevant articles reporting on IVF and intracytoplasmic sperm injection treatment outcome after ovarian stimulation using HMG or recombinant FSH plus recombinant LH. The available studies are mostly observational, using different daily doses and modes of administration. No statistically significant differences were observed in ovarian stimulation variables and clinical pregnancy and live birth rates when HMG was compared with recombinant FSH + recombinant LH. Moreover, combined analysis of all the available prospective and retrospective studies produced no firm conclusions in favour of either source of LH bioactivity. Further large randomized controlled studies are needed to investigate the effect of the LH source on IVF outcome and to identify patients who are most likely to benefit from the addition of LH bioactivity supplementation.     

Oral versus non-oral hormone replacement therapy: how important is the route of administration?

Although there are differences in the pharmacokinetic profiles of oral and non-oral routes of administration the clinical relevance of these differences remains to be determined. Likewise, there are differences in the metabolic and haemostatic effects of different routes of administration of oestrogen but these may have clinical relevance. For some parameters, such as lipids and lipoproteins, glucose and insulin metabolism, there are greater benefits from oral administration; for others, particularly haemostatic changes and effects on CRP, there are advantages from transdermal administration. For the potential benefits of HRT on CHD, these differences probably have less impact than the effect of the dose of hormones used and the lowest effective should be prescribed. Irrespective of dose, certain small sub-groups of patients should be specifically treated with an oral regimen eg those with lipid and lipoprotein abnormalities and impaired glucose tolerance whereas others should be treated with a transdermal regimen eg those with a personal or relevant family history of venous thrombosis. However, the vast majority of patients possess none of these risk factors and for them it will come down to personal preference. The availability of different combinations and doses of hormones, as well as different routes of administration, allows HRT to be tailored to the individual and there are few women for whom a suitable form of HRT cannot be found. Although data are lacking we believe it unwise to believe that fully transdermal combination therapy will not impact on risk of incident breast cancer. Based on current evidence transdermal HRT may also cause more irregular and breakthrough bleeding with sequential and continuous therapies than oral counterparts.     

Prediction of ovarian reserve based on day-3 serum follicle stimulating hormone concentrations during the pituitary suppression cycle using a gonadotropin releasing hormone agonist in patients undergoing in vitro fertilization–embryo transfer

Satisfactory results following in vitro fertilization–embryo transfer (IVF-ET) treatments depend on retrieving an appropriate number of mature oocytes without causing the development of ovarian hyperstimulation syndrome (OHSS). The present study was carried out to investigate whether the ovarian reserve is predictable based on the day-3 serum concentration of follicle stimulating hormone (FSH) during the pituitary suppression cycle using a gonadotropin releasing hormone (GnRH) agonist (defined as day-3 FSH) in patients undergoing IVF-ET treatment. Day-3 FSH before the administration of gonadotropin was assessed in 72 IVF-ET cycles from 59 infertile women. The mean?±?SD of day-3 FSH, the total amount of FSH plus human menopausal gonadotropin (hMG) administered, and the total number of oocytes retrieved was 5.5?±?2.6 mIU/ml, 2834.2?±?1236.5?IU and 7.7?±?5.8, respectively. There were significant correlations between day-3 FSH and the total amount of FSH–hMG administered (p?<?0.001), and day-3 FSH and total number of oocytes retrieved (p?<?0.001). There was a significant difference of day-3 FSH between patients who subsequently conceived (4.4?±?1.3 mIU/ml) and those who did not conceive (6.1?±?2.9 mIU/ml) (p?= 0.001). There was also a significant difference of day-3 FSH between patients who developed moderate or severe OHSS (4.5?±?1.2 mIU/ml) and those who did not (5.9?±?2.8 mIU/ml) (p?=?0.003). Receiver-operator characteristic curve analysis showed that the significant cut-off point for day-3 FSH for predicting ovarian reserve was 5.25?mIU/ml. These findings indicate that day 3-FSH is useful for predicting ovarian reserve during the pituitary suppression cycle using a GnRH agonist in patients undergoing IVF-ET.     

Antral follicle count, anti-mullerian hormone and inhibin B: predictors of ovarian response in assisted reproductive technology?

OBJECTIVE: The objective of this study was to evaluate the relationship between anti-mullerian hormone (AMH), inhibin B and antral follicle count (AFC) with ovarian response. DESIGN: Retrospective study. SETTING: Fertility unit. SAMPLE: AFC was recorded, and a serum sample obtained on day 3 from all patients undergoing in vitro fertilisation (IVF). Patients were given 300 IU/L recombinant follicle stimulating hormone (FSH; Gonal F). The following day blood samples were collected. METHODS Serum samples were assayed for FSH, AMH and inhibin B using commercial immunoassay kits and oestradiol using an in house assay. MAIN OUTCOME MEASURES: Response to gonadotrophin stimulation and the number of eggs collected. RESULTS: AFC was negatively correlated to age (r=-0.426, P < 0.001). Delta inhibin B (levels of inhibin B on day 4 minus day 3) had the best association to the number of eggs collected (r= 0.533, P < 0.001) followed by basal AMH (r= 0.51, P < 0.001) and AFC (r= 0.505, P < 0.001). The number of eggs fertilised was significantly associated with basal AMH (r= 0.592, P < 0.001) and inhibin B (r= 0.548, P < 0.001). AMH with a cutoff of 0.2 ng/mL had the best sensitivity (87%) and specificity (64%) in predicting poor response. A cumulative score using basal FSH, basal AMH, delta E2 (levels of oestradiol on day 4 minus day 3), delta inhibin B, AFC and age gives the best predictive statistics to identify poor responders with 87% sensitivity and 80% specificity and a positive likelihood ratio of 4.36. CONCLUSION: Delta inhibin B had the best positive association with the number of eggs collected and basal AMH is the single best predictor of poor response. AFC has a significant association with the number of eggs collected and is predictive of clinical pregnancy. It is evident that a single parameter is of limited value in predicting ovarian response. However, we have demonstrated a cumulative score using all the above markers could be useful in predicting poor response.     

Are recombinant gonadotrophins safer, purer and more effective than urinary gonadotrophins?

Recombinant gonadotrophins have been proposed as the gold standard for current infertility treatment. However, there is little difference between the various available urinary or recombinant gonadotrophins in terms of safety, purity or clinical efficacy. Resources committed to determining an advantage of one gonadotrophin preparation over another would be better spent on research for new treatments.     

The importance of cystoscopy and bladder biopsy in women with refractory overactive bladder: the urogynaecologist's point of view?

Objectives

To assess the sensitivity, specificity, positive and negative predictive value of cystoscopy and the clinical value of bladder biopsy in women with refractory overactive bladder (OAB) symptoms.

Study design

Prospective observational study carried out in a tertiary referral urogynaecology unit in London. Consecutive women with OAB resistant to pharmacotherapy who underwent cystoscopy, hydrodistention and bladder biopsy were studied. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of cystoscopy as well as histological findings for chronic cystitis were evaluated.

Results

106 women aged 22–91 years were studied. Histopathology showed chronic cystitis in 94 women, follicular cystitis 3, acute and chronic cystitis in 2, transitional cell carcinoma in 6 and no abnormality in 1 woman. Trabeculations and increased vascularity were the most common cystoscopic findings, seen in 71% and 72% of women respectively. Haemorrhages on first filling and haemorrhages on refilling had specificities of 86.6% and 80% respectively for chronic cystitis. Their sensitivities were 9.8% and 13.1% respectively. Trabeculations and increased vascularity had sensitivities of 68.1% and 68.1% and their specificities were 11.6% and 4.5% respectively. Trabeculations, increased vascularity, haemorrhages on first filling and haemorrhages on refilling all had a PPV over 80% for chronic cystitis.

Conclusions

More than 90% of women with refractory OAB symptoms have chronic cystitis on histopathology. Cystoscopy alone is useful, but not always adequate to diagnose chronic cystitis. Antibiotic therapy in those women might be beneficial before starting anticholinergics. Larger randomised controlled trials are mandatory to confirm our hypothesis.     

Xenotransplantation of pre-pubertal ovarian cortex and prevention of follicle depletion with anti-Müllerian hormone (AMH)

Objective

To determine whether recombinant AMH (rAMH) could prevent post-transplant follicular depletion by acting on the stemness markers Oct-4, Sox2, and NANOG.

Materials and methods

This was an experimental study where 12 ovariectomized nude mice were xenotransplanted with vitrified/warmed ovarian cortex obtained from a pre-pubertal girl and Alzet pumps delivering rAMH, or placebo (control), were inserted intra-abdominally. Previously vitrified/warmed ovarian cortex fragments were transplanted after 7 days and then harvested after 14 days from pump placement. We performed real-time RT-PCR analyses, ELISA for AMH, FSH, and estradiol, histologic measurement of ovarian follicles, and immunohistochemistry for Ki67 and TUNEL. The main outcome measures were serum levels and tissue expression of the parameters under investigation and follicle count.

Results

Serum AMH, FSH, and estradiol reflected post-ovariectomy profiles and were mildly influenced by rAMH administration. Ovarian cortex expression of AMH, AMH-R2, VEGF, GDF9, Oct-4, and Sox2 was lower in rAMH mice than in controls, while NANOG was upregulated. There was a non-significant decrease in primordial follicles after vitrification-warming, and xenotransplantation further decreased this number. There were lower cell replication and depressed apoptosis in the rAMH group.

Conclusions

Administration of recombinant AMH in the peri-transplant period did not protect the initial follicular depletion but decreased apoptosis and cellular activation and regulated stem cell markers’ tissue expression. These results aid our understanding of the inhibitory effects of AMH on follicular development and show the benefit of administering exogenous AMH at the time of pre-pubertal ovarian cortex transplant to protect the follicles from pre-activation and premature depletion.