Outcome of in vitro fertilization in patients with proven poor ovarian responsiveness after early vs. mid-follicular LH exposure: a prospective, randomized, controlled study

Objective

To compare early vs. mid-follicular exposure to LH in patients with poor ovarian responsiveness undergoing in vitro fertilization (IVF).

Design

Prospective, randomized, controlled trial.

Setting

University Hospital, University-affiliated private Clinic.

Patients

Five hundred-thirty women with poor ovarian responsiveness during the first IVF cycle, undergoing their second IVF attempt.

Interventions

In a GnRH-analogue long protocol, ovarian stimulation with recombinant FSH (300 IU/day) plus randomly assigned addition of recombinant LH (150 IU/day) from day 1 (early LH exposure; n = 264) or from day 7 (late LH exposure; n = 266).

Main outcome measure(s)

Primary outcome was the number of oocytes retrieved. Secondary outcomes were: cancellation rate, total gonadotropin dose, duration of ovarian stimulation, number of embryos available for transfer, pregnancy rate per started cycle, per OPU and per embryo transfer, implantation rate, delivered/ongoing pregnancy rate.

Results

Apart from the totally administered LH dose, that was significantly higher in the group receiving it from day 1, all parameters related to IVF outcome were non significantly different in the two groups.

Conclusions

Adding LH to FSH from day 1 or from day 7 of ovarian stimulation in a GnRH-agonist long protocol exerts comparable effects on IVF outcome in poor responders.     

Does the degree of hypothalamic-pituitary-ovarian recovery after oral contraceptive pills affect outcomes of IVF/ICSI cycles receiving GnRH-antagonist adjuvant therapy in women over 35?years of age?

Purpose

To evaluate if the degree of recovery of serum gonadotropins after oral contraceptive pills (OCP) pretreatment has an impact on ovarian response in GnRH-antagonist IVF cycles in women of advanced maternal age.

Methods

In this retrospective cohort study, we included 98 women 35–42 years undergoing their first IVF cycle receiving gonadotropins and a fixed GnRH-antagonist adjuvant protocol. Data analysis was carried out according to changes in serum FSH, LH and estradiol (E₂) levels (basal and post-OCP) divided in quartiles, and also according to absolute levels. The main outcomes were peak serum E₂, number of mature oocytes retrieved, length of stimulation, and amount of gonadotropins used.

Results

By quartile analysis, patients with the highest levels of serum gonadotropins suppression and also patients with gonadotropin rebound needed larger amounts of LH during the treatment. On the other hand, women with absolute suppression of FSH/LH had increased length of stimulation.

Conclusions

The results of this study provide data that assist in clinical management. Gonadotropin serum levels after OCP treatment provide information for optimization of supplementation with LH in GnRH-antagonist cycles in women over age 35.     

Correlation of serum Anti-Müllerian hormone concentrations on day 3 of the in vitro fertilization stimulation cycle with assisted reproduction outcome in polycystic ovary syndrome patients

Purpose

To investigate whether serum Anti- Müllerian hormone (AMH) on day 3 could predict controlled ovarian stimulation and reproductive outcomes in women with polycystic ovary syndrome.

Methods

A total of 164 PCOS patients undergoing their first IVF treatment cycle were prospectively included. Serum AMH levels on cycle day 3 was measured. The controlled ovarian stimulation and clinical outcomes for the study population were divided according to the <25th, 25 to 75th, or >75th percentile of serum day-3 AMH.

Results

Estradiol levels on hCG day and the number of retrieved oocytes significantly increased with increasing serum AMH levels, while total consumption of gonadotropin dose showed a significant decrease (P < 0.05). Fertilization rate and the number of good quality embryos were comparable among the low, average and high groups (P > 0.05). Embryo implantation rates in the high AMH group was significantly inferior to those with low and average AMH concentration (27 versus 48.8 and 50%, P < 0.01). Clinical pregnancy rates was lower in the high AMH group than that of the low and average group (45.9 versus 65 and 66.7%, P = 0.09), but this difference was only close to statistical significance. In addition, ordinal regression analysis indicated that LH level was the only independent predictor of embryo implantation rates (P = 0.017).

Conclusions

In PCOS women, AMH levels on day 3 of the IVF stimulation cycle positively predict ovarian response to gonadotrophins. However, the women with high AMH levels had a significantly decreased IR, which may be due to remarkably increased LH concentrations.     

Starting and resulting testosterone levels after androgen supplementation determine at all ages in vitro fertilization (IVF) pregnancy rates in women with diminished ovarian reserve (DOR)

Purpose

To investigate whether androgen conversion rates after supplementation with dehydroepiandrosterone (DHEA) differ, and whether differences between patients with diminished ovarian reserve (DOR) are predictive of pregnancy chances in association with in vitro fertilization (IVF).

Methods

In a prospective cohort study we investigated 213 women with DOR, stratified for age (≤38 or >38 years) and ovarian FMR1 genotypes/sub-genotypes. All women were for at least 6 weeks supplemented with 75 mg of DHEA daily prior to IVF, between initial presentation and start of 1st IVF cycles. Levels of DHEA, DHEA-sulfate (DHEAS), total T (TT) and free T (FT) at baseline (_BL) and IVF cycle start (_CS) were then compared between conception and non-conception cycles.

Results

Mean age for the study population was 41.5 ± 4.4 years. Forty-seven IVF cycles (22.1 %) resulted in clinical pregnancy. Benefits of DHEA on pregnancy rates were statistically associated with efficiency of androgen conversion from DHEA to T and amplitude of T gain. Younger women converted significantly more efficiently than older females, and selected FMR1 genotypes/sub-genotypes converted better than others. FSH/androgen and AMH/androgen ratios represent promising new predictors of IVF pregnancy chances in women with DOR.

Conclusions

DOR at all ages appears to represent an androgen-deficient state, benefitting from androgen supplementation. Efficacy of androgen supplementation with DHEA, however, varies depending on female age and FMR1 genotype/sub-genotype. Further clarification of FMR1 effects should lead to better individualization of androgen supplementation, whether via DHEA or other androgenic compounds.     

Is ABO blood type associated with ovarian stimulation response in patients with diminished ovarian reserve?

Purpose

Recent studies have explored the relationship between ABO blood type and serum markers of ovarian reserve, specifically follicle-stimulating hormone (FSH) and anti-mullerian hormone (AMH). The primary objective of this study is to investigate whether there is an association between ABO blood type and ovarian stimulation response in patients with serum markers of diminished ovarian reserve (DOR).

Methods

This is a retrospective study of all patients undergoing controlled ovarian stimulation (COS) for in vitro fertilization (IVF) between May 2010 and July 2013. Patients were sub-grouped, a priori, based on serum AMH levels: ≤1 ng/mL, ≤0.5 ng/mL and ≤0.16 ng/mL. Within each sub-group, demographic, baseline IVF characteristics and COS response parameters based on ABO blood types were compared. The number of mature oocytes retrieved was considered the primary outcome. Analysis of variance (ANOVA) and Chi-square tests were used to compare means and percentages between ABO blood types within groups.

Results

Complete data was available for 2575 patients. The mean (± SD) age and BMI of the study cohort was 38.9 (±3.97) years, 23.4 (±5.91) kg/m², respectively. The distribution of ABO blood types in the cohort was as follows: 36.8 % (A), 6.56 % (AB), 17.3 % (B), and 39.3 % (O). The demographics and baseline IVF characteristics were comparable among patients with blood types A, AB, B, and O within each AMH group. Within each AMH sub-group, no difference was found in the total days of COS, total gonadotropins administered, peak estradiol level, or number of mature oocytes retrieved based on blood type.

Conclusions

Our results suggest no association between ABO blood type and ovarian stimulation response in patients with DOR. The predictive value of ABO blood type in determining ovarian stimulation response in such patients is currently limited.

Electronic supplementary material

The online version of this article (doi:10.1007/s10815-015-0485-3) contains supplementary material, which is available to authorized users.     

Comparison of intrafollicular sperm injection and intrauterine insemination in the treatment of subfertility

Purpose

To compare the efficacy of intrafollicular sperm injection (IFI) versus intrauterine insemination (IUI) in the treatment of subfertility.

Methods

38 couples suffering primary or secondary subfertility contributed a total of 47 IUI or IFI cycles, 26 by IUI and 21 by IFI. Folliculogenesis, ovulation triggering, and IUI or IFI were performed. Motile spermatozoa were inseminated into the uterine cavity for IUI or injected into pre-ovulatory follicles for IFI. The rate of biochemical and clinical pregnancy was assessed.

Results

The rate of biochemical pregnancy/cycle for IUI was 11 % as compared to 38 % for IFI (p = 0.04). The rate of clinical pregnancy/cycle for IUI was 11 % as compared to 29 % for IFI (p = 0.26). The rate of twin pregnancy and miscarriage was low and no high order multiple gestation was observed. The rate of ectopic tubal pregnancy/cycle for IUI was 0 % as compared to 9 % for IFI (p = 0.19); no ovarian pregnancy was observed. When the analysis was confined to IFI cycles in which 2.68-6.65 million motile spermatozoa were injected/follicle (n = 10), a rate of 60 % clinical pregnancy/cycle was observed, of which 2 were ectopic.

Conclusion

Under the conditions described herein, IFI was more effective than IUI at achieving pregnancy.     

Screening for Down syndrome in dichorionic twin pregnancies conceived by in vitro fertilization (IVF): a clinical pilot study to confirm the laboratory methods

Purpose

The corrections necessary to estimate the risk for Down syndrome in twin pregnancies have been pointed out. We performed a nested controlled study to evaluate the validity of these corrections in dichorionic twins conceived by IVF.

Methods

Detailed clinical data was collected from the medical records. Twins were matched with a contemporaneous cohort of spontaneously conceived singleton pregnancies that serve as reference in a 1 to 4 ratio. All patients had their entire obstetrical care at our Hospital. The Student t-test was used for group comparisons and a p-value <0.05 was considered significant.

Results

Nineteen sets of normal twins concordant in size and with appropriate weight for gestational age were matched with 80 normal and mature newborns. Significant differences between groups were found for maternal age, gestational age at delivery and newborn weight (all p < 0.01). No statistical differences were noted for the levels of the biochemical markers expressed as multiples of the median. However, a 15 % closer approximation to the laboratory median for PAPP-A and a 10 % closer approximation to the laboratory median for free β-hCG was evident in twins when compared to the reference group.

Conclusions

These findings support the methods used to estimate the risk for Down syndrome in dichorionic twin pregnancies conceived after IVF. A future study with a larger sample size could confirm if the laboratory corrections done on the combined screening test improve the predictability of Down syndrome in dichorionic twin pregnancy conceived by IVF when compared to singleton pregnancies.     

Perceptions among infertile couples of lifestyle behaviors and in vitro fertilization (IVF) success

Purpose

To assess how patients perceive various lifestyle behaviors impact IVF success.

Methods

Cross-sectional study of heterosexual, English-speaking couples (n = 138) who completed web-based surveys during IVF treatment cycle. Perceived impact of lifestyle choices assessed by multivariable logistic regression and p-value tests for linear trend (P_t).

Result(s)

During the IVF cycle, most patients consider it helpful for women to exercise (76 %), avoid stress (87 %) and limit activity after embryo transfer (92 %). The majority of patients (62 %) consider rigorous exercise (4+ h/week) helpful and nearly one-third (32 %) perceive benefit to complete bed rest after transfer. Overall, couples with a sex-specific infertility diagnosis are more likely to consider partner’s lifestyle choices impactful: male-factor couples are more likely to consider it helpful for men to limit cellular phone use (OR:2.73,CI:1.06–7.04) and diminished ovarian reserve couples are more likely to consider it helpful for women to limit exposure to plastics (OR:2.38,CI:1.03–5.51). Patients at higher levels of education (P_t < 0.01) and income (P_t < 0.01) are less likely to consider lifestyle impactful.

Conclusion(s)

Patient perceptions of the impact of lifestyle factors on IVF success vary by sex, infertility diagnosis and socioeconomic factors. Despite counseling to the contrary, many patients perceive benefit to rigorous exercise during the IVF cycle and complete bedrest following transfer. Results provide insight into patient beliefs and highlight opportunities to improve patient education, alleviate patient anxieties and potentially improve IVF outcomes.     

Uterine fibroids are characterized by an impaired antioxidant cellular system: potential role of hypoxia in the pathophysiology of uterine fibroids

Purpose

Fibroids are the most common smooth muscle overgrowth in women. This study determined the expression and the effect of hypoxia on two potent antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT) on human fibroid cells.

Methods

Immortalized human leiomyoma (fibroid) and myometrial cells were subjected to hypoxia (2 % O₂, 24 h). Total RNA and cell homogenate were obtained from control and treated cells; CAT and SOD mRNA and activity levels were determined by real-time RT-PCR and ELISA, respectively.

Results

Fibroid cells have significantly lower antioxidant enzymes, SOD and CAT mRNA and activity levels than normal myometrial cells (p < 0.05). Hypoxia treatment significantly increased SOD activity in myometrial cells while significantly decreasing CAT activity in fibroid cells (p < 0.05). There was no significant difference in CAT mRNA levels or activity in response to hypoxia in myometrial cells. Also, there was no significant difference in SOD mRNA levels in response to hypoxia in myometrial cells.

Conclusion

This is the first report to show that uterine fibroids are characterized by an impaired antioxidant cellular enzymatic system. More importantly, our results indicate a role for hypoxia in the modulation of the balance of those enzymes in fibroid and myometrial cells. Collectively, these results shed light on the pathophysiology of fibroids thereby providing potential targets for novel fibroid treatment.     

Low testosterone levels in women with diminished ovarian reserve impair embryo implantation rate: a retrospective case-control study

Objective

To investigate the association of basal testosterone (T) levels with the outcome of in vitro fertilization (IVF) in women with diminished ovarian reserve (DOR).

Methods

Complete clinical data on the first 223 IVF cycles in women with DOR were retrospectively analyzed. The associations of basal follicle stimulating hormone, luteinizing hormone, estradiol, and T levels with ovarian response and IVF outcome were studied.

Results

Basal T levels were significantly different between pregnant and non-pregnant women. However, basal T levels showed no correlation with controlled ovarian hyperstimulation parameters after adjusting for age. The association of basal T levels with pregnancy rate was significant after adjusting for other impact factors. Using receiver operating characteristic (ROC) analysis, the basal T level of 1.115 nmol/L for predicting pregnancy outcome had a sensitivity of 82.80 % and specificity of 58.09 %. The women were divided into two groups based on this value; although the clinical characteristics and ovarian stimulation parameters were similar, the clinical pregnancy (16.18 % (11/68) vs. 40.15 % (53/132), respectively, p = 0.000) and implantation rates (10.07 % (15/149) vs. 22.41 % (65/290), respectively, p = 0.002) were significantly different in the low and high T level groups.

Conclusion

In women with DOR, the basal T level presented a positive association with pregnancy outcome in IVF. The poor reproductive outcome observed in women with lower basal T levels may be due to the decreased implantation rate.     

Basal serum testosterone levels correlate with ovarian response but do not predict pregnancy outcome in non-PCOS women undergoing IVF

Purpose

To evaluate basal testosterone (T) levels in women undergoing in vitro fertilization (IVF) cycles and examine the association between basal T levels and ovarian response or IVF pregnancy outcome.

Methods

We retrospectively analyzed 1413 infertile Chinese women undergoing their first IVF treatment at our institution’s reproductive center from March 2011 to May 2013. The basal testosterone (T) levels in women undergoing in vitro fertilization (IVF) and the relationship between basal T levels and ovarian response or IVF pregnancy outcome were determined. These patients did not have polycystic ovary syndrome (PCOS) or endometriosis, and were treated with a long luteal down-regulation protocol. Subjects were divided into 2 groups according to basal testosterone (T) levels: Group 1, basal T values <20 ng/dl (n = 473), and Group 2, basal T values >20 ng/dl (n = 940). We evaluated the association of basal T levels with ovarian response and IVF outcome in the two groups.

Results

In this study, BMI, basal follicle-stimulating hormone (FSH) levels, basal luteinizing hormone (LH) levels, antral follicle count (AFC), days of stimulation, total gonadotrophin dose, basal FSH/LH ratio, and the number of follicles >14 mm were significantly different (P < 0.05) between the two groups. Basal T level positively correlated with ovarian reserve function, number of follicles >14 mm on human chorionic gonadotrophin (HCG) day, and total gonadotropin dose. However, basal T levels play no role in predicting IVF pregnancy outcome.

Conclusion

Basal T level can be used as a good predictor for ovarian response and the number of large follicles on HCG day. Additionally, we may use basal T level as a marker to predict FSH dosage. In general women, lower level of T might relate with potential poor ovarian response. However, based on our data, basal T levels do not predict pregnancy outcome.     

Serum anti-Mullerian hormone levels correlate with ovarian response in idiopathic hypogonadotropic hypogonadism

Purpose

The role of serum AMH levels in prediction of ovarian response in idiopathic hypogonadotropic hypogonadism (IHH) was evaluated.

Material method(s)

Twelve patients with IHH underwent controlled ovarian hyperstimulation (COH) for IVF were enrolled in this prospective study. Serum AMH levels were studied on the 2nd or 3rd day of an induced menstrual cycle by a preceding low-dose oral contraceptive pill treatment. A fixed dose (150–300 IU/day) of hMG was given in all COH cycles. Correlations between serum AMH levels, COH outcomes and embryological data were investigated.

Results

Mean serum AMH levels was 3.47 ± 2.15 ng/mL and mean serum peak estradiol was 2196 ± 1705 pg/mL. Mean number of follicles >14 mm, >17 mm on hCG day and MII oocytes were 4.14 ± 3.2, 4 ± 2.5 and 7.28 ± 3.5, respectively. Mean number of grade A embryos and transferred embryos were 3.28 ± 2.4 and 2.5 ± 0.7, respectively. The clinical pregnancy rate per patient was 41.6 % (5/12). Positive correlations were observed between serum AMH levels and MII oocytes (r = 0.84), grade A embryos (r = 0.85), serum peak estradiol levels (r = 0.87), and number of follicles >14 mm (r = 0.83) and >17 mm (r = 0.81) on hCG day, respectively.

Conclusion

AMH appears as a promising marker of ovarian response in patients with IHH undergoing IVF.     

Impact of assisted reproduction treatments on Spanish newborns: report of 14,119 pregnancies

Purpose

To investigate neonatal malformation, prematurity, and stillbirth in singleton and multiple pregnancies derived from different Assisted Reproductive Techniques (ART).

Methods

In this prospective cohort study data were collected, from private and public Spanish IVF units, during the years 2008 and 2009. During this period, 8,682 pregnancies were analysed from the initial 14,119 pregnancies reported. Pregnancies included in the study derived from IUI (n = 1,065), IVF (n = 838), ICSI (n = 5,080), FET (n = 1,404) and PGD (n = 295). This first analysis focuses primarily on neonatal malformation, prematurity, and stillbirth both in singleton and multiple pregnancies derived from different ART. Malformations were classified according to the WHO ICD 10 code.

Results

Malformations were found in 0.83 % of our newborns. No differences in malformations were observed between singletons or multiples independently of the ART used. There was a significant difference in prematurity rate among singletons depending on treatment but this association was not observed in multiple pregnancies. Stillbirth was significantly lower in singleton (0.72 %) than in multiple pregnancies (1.82 %).

Conclusions

The percentage of malformations observed in ART newborns was similar to the rate observed in the normally-conceived Spanish population. Multiplicity seems to be the most important factor associated with an increased incidence of newborn complications such as prematurity or stillbirth.     

Supernumerary Blastocyst Cryopreservation: A key Prognostic Indicator for Patients Opting for an Elective Single Blastocyst Transfer (eSBT)

Objective

To determine if patients, less than 40 years of age with or without day 5 cryopreservation (d5 cryo), compromise their pregnancy rate (PR) by choosing an eSBT.

Design

Retrospective analysis

Setting

University IVF center

Patients

2,203 non-donor fresh IVF cycles in women <40 years of age from January 2004 to January 2010.

Interventions

None

Main outcome measure(s)

Eggs retrieved, Embryos cryopreserved, Implantation Rates, Clinical Pregnancy Rates, Live Birth Rates, Spontaneous Abortion Rates

Results

Pregnancy outcomes in women <40 years with or without d5 cryo were compared according to whether patients underwent an eSBT versus a 2BT in non-donor fresh IVF cycles. Overall, eSBT was associated with elimination of twinning while maintaining a high clinical pregnancy rate in both groups with d5 cryo (75 % eSBT versus 72 % 2BT) and groups without d5 cryo (48 % eSBT versus 56 % 2BT).

Conclusions

In this study, patients <40 years of age have eliminated twinning by electively choosing to transfer a single blastocyst without compromising their PR if embryos are available for d5 cryo, and suffer only a non-statistically significant drop in their PR if there are no embryos available for d5 cryo in exchange for the benefit of eliminating the obstetrical risk of twinning.     

Phthalates and bisphenol do not accumulate in human follicular fluid

Objective

To determine if phthalates and bisphenol A accumulate in human follicular fluid after brief exposure to medical plastics during an IVF cycle

Study design

Prospective collection of follicular fluid from five infertile women undergoing oocyte retrieval at a University IVF laboratory and analysis of Phthalate & Bisphenol A levels.

Results

All phthalate levels were detected at levels less than 15 ng/mL and Bisphenol A levels were undetectable in all five samples. The concentrations of phthalates are 200–1000 fold less than the minimum levels reported to cause reproductive toxicity in vitro to cumulus-oocyte complexes of laboratory animals.

Conclusions

In reproductive age women undergoing infertility treatments there is little transfer or accumulation of phthalates, phthalate metabolites or bisphenol A into the microenvironment of the human preovulatory oocyte and the levels are not clinically significant. Further investigation of phthalate and bisphenol A accumulation in vivo in human follicular fluid may not be productive.     

MILD ovarian stimulation with GnRH-antagonist vs. long protocol with low dose FSH for non-PCO high responders undergoing IVF: a prospective, randomized study including thawing cycles

Objective

To compare the effectiveness of two stimulation protocols in non-polycystic ovary (PCO) high responders undergoing in vitro fertilization (IVF).

Design

Prospective randomized trial.

Setting

A Reproductive Medicine and IVF Unit of a University Hospital and a private IVF Clinic.

Methods

Four hundred-and-twelve normoovulatory women with good ovarian responsiveness were randomized to receive either the “mild” (FSH 150 IU/day from day 4 of a spontaneous cycle followed by GnRH-antagonist from day 8; n = 205) or the “long” (FSH 150 IU/day; n = 207) stimulation protocol. The outcome of these two regimens was compared including “fresh” and thawing cycles.

Results

The total FSH dose and the peak estradiol level were significantly lower in the “mild” protocol, whereas the retrieved oocytes, fertilization rate, number and quality of embryos, pregnancy and implantation rates, cumulative “fresh plus thaw” success rate, and incidence of severe ovarian hyperstimulation syndrome were comparable with the two regimens.

Conclusions

In young, normoovulatory patients with good ovarian responsiveness undergoing IVF the “mild” stimulation protocol has effectiveness and risks comparable to the “long” protocol with low FSH starting dose, even when thawing cycles are included in the comparison.     

Human chorionic gonadotropin (hCG) plasma levels at oocyte retrieval and IVF outcomes

Purpose

The aim of our study was to ascertain the influence of hCG levels at oocyte pick-up on IVF outcomes, and their relationship with clinical parameters.

Methods

A prospective study was performed including 473 women undergoing IVF, aged under 40 years. Blood samples to analyze hCG levels were obtained at the time of follicular aspiration, 36 h after the administration of 250 μg of recombinant hCG.

Results

Neither the numbers of oocytes obtained or fertilized, nor the pregnancy rate, were correlated with hCG levels. Moreover, hCG values were very similar in women who did and did not become pregnant (123.3 ± 48.7 and 117.5 ± 44.7 mUI/mL). Cases in which no oocytes were recovered after follicular aspiration had similar hCG levels to those in which more than 1 oocyte was obtained. On the other hand, hCG levels were negatively related to body mass index, weight, and age.

Conclusions

These data indicate that after the administration of 250 μg of recombinant hCG, hCG levels are not responsible for failure to recover oocytes. Specifically, there was no correlation between plasma hCG levels and the number of oocytes obtained or other markers of IVF outcome. There was, however, an inverse relationship with BMI, body weight and age.     

The ovarian response to standard gonadotrophin stimulation depends on FSHR, SHBG and CYP19 gene synergism

Purpose

Follicle stimulating hormone, sex hormone-binding globulin and cytochrome P450 aromatase play crucial roles in the regulation of mammalian reproduction. The synergistic effect of FSHR 307(T/A)/FSHR 680(N/S), SHBG(TAAAA)_n and CYP19(TTTA)_n genotypes on ovarian response to standard gonadotrophin stimulation of women undergoing medically assisted reproduction (IVF/ICSI) was explored.

Methods

The study population consisted of 300 women under IVF/ICSI treatment and 300 women with at least with at least one successful child birth as controls. The polymorphisms were genotyped while the follicular size, the follicle and oocyte numbers were recorded during oocyte retrieval.

Results

The genotype analysis, excluding heterozygotes for each particular polymorphism, revealed eight combined homozygotic FSHR/SHBG/CYP19 genotypes. A gradual reduction in the number of follicles and oocytes from FSHR 307Thr/680Asn allele/long SHBG allele/long CYP19 allele homozygotes to FSHR 307Ala/680Ser allele/short SHBG allele/short CYP19 allele homozygotes was observed (20.36 ± 6.74 vs. 8.05 ± 2.47, p < 0.008 and 13 ± 4.63 vs. 6.1 ± 2.32, p < 0.02, respectively).

Conclusions

FSHR/SHBG/CYP19 combined genotypes are associated with ovarian response to standard gonadotrophin stimulation of women undergoing medically assisted reproduction.     

Rescue in vitro fertilization using a GnRH antagonist in hyper-responders from gonadotropin intrauterine insemination (IUI) cycles

Objective

To evaluate the outcomes in the conversion of high-response gonadotropin intrauterine insemination (IUI) cycles to “rescue” in vitro fertilization (IVF) using a Gonadotropin-Releasing Hormone (GnRH) antagonist, with regards to implantation rates, pregnancy rates, cost, and ovarian hyperstimulation syndrome (OHSS) as compared to matched, hyper-responder, IVF controls.

Methods

This prospective cohort study was conducted between January 2007 and December 2009 at our institution. In order to decrease high-order multiple pregnancy, minimize the incidence of OHSS, and avoid cycle cancellation, high-response stimulated-IUI patients opted to convert to “rescue” IVF using the GnRH antagonist cetrorelix acetate. We then compared their clinical outcomes with matched patients from high-response IVF cycles of the standard long mid-luteal GnRH agonist protocol (14 or more collected oocytes). Only cases of conventional IVF without intra-cytoplasmic sperm injection (ICSI) were included in the control group.

Results

Out of 184 patients undergoing stimulated-IUI cycles with gonadotropins, 87 patients developed a hyper-response, and 20 opted to convert to “rescue” IVF. These patients were compared with 157 matched, hyper responder IVF controls from our registry. The implantation rate was 25.6 % in the “rescue” IVF group and 20.7 % in the control IVF group (p < 0.0047). The ongoing clinical pregnancy rate per embryo transfer was 45.0 % and 33.6 % in the “rescue” IVF and the control IVF groups, respectively (p < 0.0001). The mean duration of stimulation was comparable between cohorts (10.0 vs.10.4 days, p = 0.6324). The mean dose of gonadotropin used per cycle was higher in the control group, 2664 international units (IU) of follicle stimulation hormone (FSH) compared to 1450 IU of FSH in the “rescue” IVF group (p < 0.0001). The incidence of severe OHSS is also higher in the control group, 5.1 % versus no cases in the “rescue” IVF group (p < 0.0001).

Conclusion

Our study demonstrates that conversion of high-response gonadotropin-IUI cycles to “rescue” IVF using a GnRH antagonist is a cost-effective strategy that produces better results than regular IVF with relatively minimal morbidity, and shorter duration to achieve pregnancy. Implantation and ongoing clinical pregnancy rates tend to be higher than those from hyper-responder regular IVF patients.     

Utilization rates and results of long-term embryo cryopreservation before gonadotoxic treatment

Purpose

The aim of this study was to evaluate long-term embryo cryopreservation, utilization, and success rate in patients subjected to gonadotoxic treatments in the context of cancer.

Methods

This is a retrospective study on patients (n = 54) undergoing ovarian stimulation and IVF for fertility preservation between January 1997 and June 2014. Embryos were slow-frozen and stored until the women were cured and able to undergo embryo transfer.

Results

Fifty-four women underwent 66 oocyte pick-up procedures in total, and embryos were obtained from 52 of the 54 patients. Four patients died before their frozen embryos could be thawed. Of the remaining 48, 9 women returned to use their embryos, resulting in 6 pregnancies (66 % cumulative pregnancy rate), two of which ended in miscarriage. The live birth rate per patient was thus 44 % (4/9). The true come-back rate, calculated after applicable exclusions, was found to be 23 %.

Conclusion

IVF followed by embryo freezing is a widely established technique for fertility preservation, but little has been published on the outcomes in cancer patients. While we found the number of good-quality embryos to be lower than in a normal population, the cumulative live birth rate was similar to that achieved with fresh embryos in non-cancer patients. The utilization rate of this fertility preservation method can be considered high.