Assisted reproduction counseling in women aged 40 and above: a cohort study

Purpose

Fertility treatment in women aged ≥40 year old remains difficult and controversial. All available studies in older women report results of one specific method of ART, i.e. IUI, IVF/ICSI or oocyte donation, and success rates are always published per attempt but never per patient. Randomized studies are not available because of the obvious heterogeneity in patient populations and treatment options. This prospective observational study aimed at analyzing the outcome in a consecutive cohort of patients above 40 undergoing various methods of ART.

Methods

A total number of 909 women older than 40 attended our fertility centre during a 3 years period. A flowchart showing the consecutive ART treatments with their respective outcome was constructed. Any delivery after 22 weeks gestation (or 500 g.) was taken as primary endpoint. Crude cumulative delivery rates (CDRs) and binomial exact 95 % confidence limits (95 % CLs) were calculated for each group of interest.

Results

ART treatment could be proposed to 737 patients (81 %) and eventually 585 patients (64 %) started ART treatment: 111 patients started IUI, 439 patients started IVF/ICSI and 35 patients started oocyte donation as a primary approach ART. Ten patients got pregnant spontaneously and delivered before starting any treatment. In the 909 patients consulting for infertility, 111 deliveries were achieved after ART, i.e. a crude CDR of 12.2 % (95 % CL 10.1 % to 14.5 %).

Conclusion

Only 10 % of patients aged 40 and above could achieve delivery of their genetically-own child, while 1 % conceived spontaneously. More than one third of patients consulting never started any treatment for different reasons, i.e. anticipated poor prognosis, financial restrictions, illness or spontaneous pregnancy.     

Homologe intrauterine Insemination

Background

The aim of this retrospective study was to evaluate homologous intrauterine insemination (IUI) before in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).

Patients and methods

A total of 448 patients were included. Data were collected from 1,086 treatment cycles.

Results

The live birth rate (BTH rate) was about 17% per couple. About 87% of all live births were achieved within the first three IUI cycles (P=0.05). A significantly better likelihood of pregnancy was found for patients with polycystic ovarian syndrome PCOS (P<0.05). Patients who were not tested for their tubal patency achieved a higher BTH rate compared to patients undergoing this investigation (P<0.05).

Conclusion

Using a minimally invasive method with easy handling and little psychological distress compared to IVF/ICSI, IUI should be a first step in infertility treatment. An evaluation of tubal patency beforehand seems indicated only if there is a specific patient history.     

The role and place of the assisted reproductive technology (ART) in treatment of infertility

The assisted reproductive technics (ART) compose the very valuable tool in the infertility treatment additionally to pharmacological and surgical methods. ART comparises the classical in vitro fertilization and embryotransfer (IVF/ET) intracytoplasmic sperm injection (ICSI) intrauterine insemination (IUI), microepididymal sperm spiration (MESA), and testicular sperm aspiration (TESA). Male infertility, tubal factor, ovarian factor, endometriosis or an unexplained infertility constitute pathologies where ART can be applied as the methods of choice or as the methods of the last chance. The efficacy of ART is closely related to the age of the female partner. Hence, taking a decision of the inappropriate treatment of the infertility and prolongation of such treatment for years is the "Theft" of the reproductive time of women and a diminution or even deprivation of the chance for pregnancy. The role and the appropriate time of the ART application in different infertility causes are described.     

A comparison of post-thaw results between embryos arising from intracytoplasmic sperm injection using surgically retrieved or ejaculated spermatozoa

OBJECTIVE: To study the effect of freeze-thaw on embryos derived from intracytoplasmic sperm injection (ICSI) using surgically retrieved and ejaculated spermatozoa. DESIGN: Retrospective study. SETTING: Private IVF center. PATIENT(S): Three hundred eighty-three patients undergoing frozen-thawed ET cycles. INTERVENTION(S): Testicular sperm aspiration (TESA) or percutaneous epididymal sperm aspiration (PESA) were the sperm surgical retrieval methods used for ICSI. Embryos resulting from ICSI using surgically retrieved and ejaculated spermatozoa were frozen, thawed, and transferred. MAIN OUTCOME MEASURE(S): Post-thaw survival, implantation, and pregnancy rates. RESULT(S): No differences were found between the ejaculated sperm and TESA/PESA groups in terms of post-thaw survival rate (68.4% vs. 66.1%, respectively), pregnancy rate (20.1% vs. 16.1%), and implantation rate (10.6% vs. 12.7%). Similar results were found for those variables when comparing TESA and PESA groups. CONCLUSION(S): Cleavage embryos arising from ICSI cycles using testicular and epididymal spermatozoa can be frozen with survival, pregnancy, and implantation rates comparable to those obtained with ejaculated spermatozoa.     

Conventional IVF versus ICSI in sibling oocytes from couples with endometriosis and normozoospermic semen

Purpose

This study compares the fertilization rate and embryonic development of oocytes randomly inseminated by conventional IVF or ICSI in patients with endometriosis and normozoospermic semen during IVF cycles.

Methods

Sibling oocytes were randomized to be inseminated either by ICSI or IVF. Rates of fertilization, cleavage, blastulation and embryonic morphology were assessed.

Results

A total of 786 sibling cumulus-oocyte complexes (COC) were randomized between insemination by conventional IVF (387 COC) or ICSI (399 COC). A significantly higher fertilization rate was found in the ICSI group (ICSI versus IVF, 73.3±23 % versus 54.7±31.9 % respectively; P=0.003), yielding a higher mean number of day 2 embryos (5.2±3.4 versus 3.6±2.9 respectively; P=0.002). Triploid fertilization rate (3PN/COC) was significantly higher in the IVF group compared to the ICSI group (3.9±8.7 % versus 0.9±3.1 % respectively; P=0.02). The morphology score and rate of development of day 2 and 3 embryos were not different between the two groups. Comparison of embryo transfer cycles in which either IVF or ICSI only embryos were transferred did not reveal any statistically significant differences in pregnancy or implantation rates.

Conclusion

ICSI appears to be a better treatment option than conventional IVF in endometriosis-associated infertility, since it offers the advantages of higher fertilization rate and mean number of embryos and lower rate of total fertilization failure and triploid fertilization.     

Percutaneous epididymal sperm aspiration and short time insemination in the treatment of men with obstructive azoospermia

Objective

To study the efficacy of percutaneous epididymal sperm aspiration (PESA) in combination with short time insemination to treat infertile men with obstructive azoospermia (OA).

Design

Paired randomized controlled trial in which each couple’s cohort of oocytes was divided into two equal groups.

Setting

Center for reproductive care.

Patients

Twenty men with OA.

Interventions

Motile spermatozoa were collected using PESA. Half of the oocytes were used for intracytoplasmic sperm injection (ICSI). The rest were inseminated briefly with PESA sperm in vitro fertilization (IVF). After 4–5 h, the remaining cumulus cells were removed mechanically for second polar body observation to decide whether to apply “rescue” ICSI (RE-ICSI).

Main outcome measures

Rates of oocyte maturation, fertilization, cleavage, and good quality embryos. Numbers of available embryos and good quality embryos were compared between PESA-IVF (using a short incubation protocol + rescue ICSI) group and PESA-ICSI group.

Results

In the short time insemination group, cumulus cells were dispersed by PESA spermatozoa. No second polar bodies were found, so RE-ICSI was done. PESA-IVF + RE-ICSI and PESA-ICSI outcomes were comparable in terms of fertilization rates, 2PN cleavage rate and good quality embryo rates with no statistically significant differences.

Conclusions

PESA sperm without centrifugation could disperse the cumulus cells but were infertile and therefore could substitute for synthetic hyaluronidase. The outcomes of PESA-IVF with rescue ICSI were equivalent to PESA-ICSI. Using spermatozoa obtained by PESA and IVF before RE-ICIS is a viable treatment for men with OA.     

Treatment of unexplained and mild male factor infertility by In Vitro fertilization and intra-uterine insemination

Objectives

To evaluate the efficacy of in vitro fertilization (IVF) and intra-uterine insemination (IUI) in couples with unexplained and mild male factor infertility.

Methods

One hundred fifty couples were allocated to treatment with IVF and IUI, both following the same protocol (clomiphene citrate and follicle stimulating hormone (FSH) injection) depending upon their hormonal response. The mild male factor patients were included in the study because we observed that their rate of failed fertilization was not different from those in couples with unexplained infertility. They had ovulatory cycles confirmed by recent ovulatory mid luteal phase progesterone measurement and bilateral tubal patency, which was confirmed by laparoscopy or hysterosalpingography. Men with unexplained infertility had semen analysis with a sperm concentration ≥25×10⁶/ml, motility (grdel + 2) ≥40% and normal forms ≥25%. Men with mild male factor infertility had semen analysis where only one of the above parameters was below the normal range.

Results

Among the 150 couples, 75 were treated with IVF and 75 were treated with IUI. The mean age of women allocated to IVF was 32.9 years compared to 33.2 years for the IUI treatment group. Cycle day 2 basal plasma estradiol, LH and FSH concentrations were also not different (geometric means; Estradiol 244 and 245 pmol/1, LH 4.9 and 5.3 IU/1, FSH 7.5 and 7.7 IU/1 in the IVF and IUI treatment groups, respectively).

Conclusion

IUI is the first choice of treatment for unexplained and mild male factor infertility with a lower cost and the equal efficacy as IVF. Treatment delivered within the context of a specialized IVF center will be more efficient and safer because of the potential to salvage over-responding cycles by conversion to IVF.     

Surgically acquired sperm use for assisted reproductive technology: trends and perinatal outcomes,USA, 2004–2015

Purpose

To compare national trends and perinatal outcomes following the use of ejaculated versus surgically acquired sperm among IVF cycles with male factor infertility.

Methods

This retrospective cohort includes US fertility clinics reporting to the National ART Surveillance System between 2004 and 2015. Fresh, non-donor IVF male factor cycles (n?=?369,426 cycles) were included. We report the following outcomes: (1) Trends in surgically acquired and ejaculated sperm. (2) Adjusted risk ratios comparing outcomes for intracytoplasmic sperm injection (ICSI) cycles using surgically acquired (epididymal or testicular) versus ejaculated sperm. (3) Outcomes per non-canceled cycle: biochemical pregnancy, intrauterine pregnancy, and live birth (≥?20 weeks). (4) Outcomes per pregnancy: miscarriage (<?20 weeks) and singleton pregnancy. (5) Outcomes per singleton pregnancy: normal birthweight (≥?2500 g) and full-term delivery (≥?37 weeks).

Results

Percentage of male factor infertility cycles that used surgically acquired sperm increased over the study period, 9.8 (2004) to 11.6% (2015), p?<?0.05. The proportion of cycles using testicular sperm increased significantly over the study period, 4.9 (2004) to 6.5% (2015), p?<?0.05. Among fresh, non-donor male factor ART cycles which used ICSI (n?=?347,078 cycles), cycle, pregnancy, and perinatal outcomes were statistically significant but clinically similar with confidence intervals approaching one between cycles involving epididymal versus ejaculated sperm and between testicular versus ejaculated sperm. Results were similar among cycles with a sole diagnosis of male factor (no female factors), and for the subset in which the female partner was <?35 years old.

Conclusion

Among couples undergoing ART for treatment of male factor infertility, pregnancy and perinatal outcomes were similar between cycles utilizing ejaculated sperm or surgically acquired testicular and epididymal sperm.

     

Chronic hepatitis B virus infection in women is not associated with IVF/ICSI outcomes

Objective

This study was to evaluate whether chronic HBV (Hepatitis B virus) infection in women is associated with poor performance following IVF/ICSI (in vitro fertilization/intracytoplasmic sperm injection) treatments.

Materials and methods

123 cycles with female chronic HBV infection were compared with 246 cycles with no-infected couples, matched for female age, D3 serum FSH (follicles stimulation hormone) levels, body mass index and assisted reproductive technology approach used (IVF or ICSI), in a ratio of 1:2.

Results

The details in IVF/ICSI cycles, including the dosage of gonadotrophin used, the serum estradiol levels and the endometrial thickness on the day of hCG (human chorionic gonadotrophin) injection, the mean number of oocytes retrieved, and the embryology data, were similar among seropositive and seronegative women. And there was no significant differences in implantation rates and live birth rates between seropositive women group and matched control (30.52 versus 28.34 % per transfer; 42.28 versus 40.65 %).

Conclusions

The results indicated that women with chronic HBV infection is not associated with outcomes of IVF/ICSI treatments.     

Genetic screening in Italian infertile couples undergoing intrauterine insemination and in vitro fertilization techniques: a multicentric study

Aim of the study.?To report the frequency of aberrant karyotype and mutated cystic fibrosis transmembrane conductance regulator (CFTR) gene, according to a careful application of Italian guidelines for genetic screening in infertile couple candidates for intrauterine insemination (IUI) and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI).

Materials and methods.?Two thousand and sixteen consecutive infertile couple candidates for Assisted Reproduction Techniques (ART) were screened for karyotype and 616 couples for CFTR analysis.

Results.?Regarding karyotype analysis, 59 chromosomal abnormalities were diagnosed in candidates for IVF/ICSI: 27 mutations in women corresponding to a frequency equal to 1.53% (27/1762; 95% confidence interval [CI], 0.96–2.1%) and 32 mutations in men corresponding to a frequency equal to 1.82% (32/1762; 95% CI, 1.2–2.44%) for men. The frequency differs according to the sperm count. In couple candidates for IUI techniques, no genetic abnormalities were found in male patients and only one aberration in a female patient with a frequency of 0.41% (1/245 CI 0.01–0.81%). Regarding CFTR analysis, excluding the 5T variant, we obtained 20 mutations in couples undergoing IVF/ICSI and 8 mutations in IUI group.

Conclusion.?Couples undergoing IVF/ICSI show a higher prevalence of aberrant karyotypes than general population, whereas the frequency of a mutation of the CFTR gene is similar. On the other hand, couples undergoing IUI do not differ from the general population either for karyotype or for CFTR mutations.     

Sperm DNA fragmentation index,as measured by sperm chromatin dispersion,might not predict assisted reproductive outcome

Objective

Routine semen parameters have limited clinical diagnostic value for predicting male infertility. The aim of this study was to investigate the association between sperm DNA fragmentation index (DFI) and semen quality, and between DFI and clinical pregnancy rate of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).

What is the best treatment option for infertile women aged 40 and over?

Purpose

To summarise the causes of decreased fecundity with age and review chronological vs biological ovarian ageing. To explore the clinician’s means of assessing a woman’s ovarian reserve. To review the recent literature on the effectiveness of different assisted reproductive technology (ART) techniques for women aged 40 and over and offer a single best treatment option.

Methods

Pubmed and google scholar were searched for relevant articles using key words. Data were extracted based on authors, year, aims, sample and results.

Results

Success rates for women aged 40 or over with clomiphene, IUI, IUI with FSH are all extremely low, at less than 1 % live birth per cycle. However, IVF offers a success rate of around 13.7 % per cycle.

Conclusion

An exploration of the effectiveness of available treatment options for older infertile women using their own gametes suggests that IVF offers the best prospects of success. Attempting treatments other than IVF will delay conception unnecessarily.     

Kinderwunsch der Frau ab 40 Jahren

Spontaneous conception

Infertility 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 fertilization

Intrauterine 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.     

Effect of the total motile sperm count on the efficacy and cost-effectiveness of intrauterine insemination and in vitro fertilization

OBJECTIVE: To determine prognostic factors for achieving a pregnancy with intrauterine insemination (IUI) and IVF. To compare the effectiveness and cost-effectiveness of IUI and IVF based on semen analysis results. DESIGN: Retrospective cohort study. SETTING: Academic university hospital-based infertility center. PATIENT(S): One thousand thirty-nine infertile couples undergoing 3,479 IUI cycles. Four hundred twenty-four infertile couples undergoing 551 IVF cycles.Intervention(s): IUI and IVF treatment. MAIN OUTCOME MEASURE(S): Multiple logistic regression analysis was used to assess the significance of prognostic factors including a woman's age, gravidity, duration of infertility, diagnoses, use of ovulation induction, and sperm parameters for predicting the outcomes of clinical pregnancy and live birth rate after the first cycle of IUI and IVF. The relative effectiveness and cost-effectiveness of these treatments were then determined based on sperm count results. RESULT(S): Female age, gravidity, and use of ovulation induction were all independent factors in predicting pregnancy after IUI. The average total motile sperm count in the ejaculate was also an important factor, with a threshold value of 10 million. For IVF, only female age was an important predictor for both clinical and ongoing pregnancy. When the average total motile sperm count was under 10 million, IVF with ICSI was more cost-effective than IUI in our clinic. CONCLUSION(S): An average total motile sperm count of 10 million may be a useful threshold value for decisions about treating a couple with IUI or IVF.     

Aneuploidy in abortuses following IVF and ICSI

Purpose

To compare aneuploidy rates in first trimester pregnancy losses following IVF ± ICSI.

Methods

A retrospective cohort analysis of karyotypes of abortuses following conventional IVF (n = 159) and ICSI (n = 196).

Results

50.1% of losses were found to be cytogenetically abnormal among all patients undergoing IVF ± ICSI. A significant increase in fetal aneuploidy rate was noted with increasing maternal age (<30 years = 26.1% vs. 31 to 34 years. = 38.2% vs. 35 to 39 years. = 51.3% vs. >39 years. = 65.9%). Aneuploidy rates were similar in the ICSI vs. conventional IVF groups (52.6% vs. 47.2% [p 0.31, RR 1.11, 95% CI 0.90, 1.38]). More sex chromosome anomalies were noted in the ICSI group.

Conclusions

The aneuploidy rate in first trimester abortuses significantly increases with increasing maternal age. ICSI was not shown to significantly increase the aneuploidy rate. However, more sex chromosome anomalies were found among pregnancies resulting from ICSI.     

Controlled ovarian hyperstimulation and intrauterine insemination for treatment of unexplained infertility should be limited to a maximum of three trials

OBJECTIVE: To investigate the optimum number of cycles of controlled ovarian hyperstimulation and intrauterine insemination in the treatment of unexplained infertility. DESIGN: Observational prospective study. SETTING: In vitro fertilization embryo transfer center. PATIENT(S): Five hundred ninety-four couples with unexplained infertility. INTERVENTION(S): Controlled ovarian hyperstimulation (COH), intrauterine insemination (IUI), in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI). MAIN OUTCOME MEASURE(S): Cycle fecundity. RESULT(S): One to 3 cycles of COH/IUI were performed in 594 patients (group A) undergoing 1,112 cycles (mean, 1.9 cycles/patient). Up to 3 further trials (cycles 4-6) of COH/IUI were then performed in 91 of these women (group B), a total of 161 cycles (mean, 1.8 cycles/patient). A historical comparison group C consisted of 131 patients with 3 failed cycles of COH/IUI who underwent 1 cycle of IVF and ICSI at our center. In group A, 182 pregnancies occurred, with a cycle fecundity of 16.4% and a cumulative pregnancy rate (PR) of 39.2% after the first 3 cycles. In group B, 9 pregnancies occurred in cycles 4-6, with a cycle fecundity of 5.6%, significantly lower than that of group A (P<.001). The cumulative PR rose to 48.5% by cycle 6, a further increase of only 9.3%. In the women undergoing IVF and ICSI in group C, 48 pregnancies occurred, with a cycle fecundity of 36.6% per cycle, significantly higher than that of group B (P<.001). CONCLUSION(S): In unexplained infertility, the cycle fecundity in the first three trials of COH and IUI was higher than in cycles 4-6, with a statistically significant difference. Patients should be offered IVF or ICSI if they fail to conceive after three trials of COH and IUI.     

Vitamin D improves endometrial thickness in PCOS women who need intrauterine insemination: a randomized double-blind placebo-controlled trial

Purpose

To determine whether administration of vitamin D affects the success rates of intra uterine insemination (IUI) in infertile polycystic ovarian syndrome (PCOS) women and their endometrial thickness.

Methods

This randomized, double-blind, placebo-controlled trial was conducted in an infertility clinic of Women’s Hospital, and 110 infertile PCOS patients undergoing IUI were randomly divided to receive vitamin D or placebo. Endometrial thickness, IUI results, number of dominant follicles, duration of IUI cycle, and dose of HMG used in IUI were determined.

Results

The endometrial thickness was significantly different in the group treated with vitamin D versus the placebo group (p = 0.003). There was no statistical difference in pregnancy out come between the two groups (RR = 1.167, CI 95 % 0.70–1.93). No statistical difference was found in number of dominant follicles (p = 0.96), duration of IUI cycles (p = 0.70) and dose of HMG used for IUI (p = 0.95).

Conclusions

It seems that administration of vitamin D induces endometrial proliferation in PCOS women during IUI cycle.     

Ongoing pregnancy after ICSI of frozen-thawed PESA-retrieved spermatozoa and IVF in a controlled natural cycle

The recovery of a mature oocyte from a natural cycle followed by IVF (nIVF) is an attractive alternative to conventional IVF, involving ovarian stimulation, in the treatment of female infertility. Similarly, surgical recovery of spermatozoa from the epididymis by percutaneous sperm aspiration (PESA) has simplified the treatment of men with obstructive azoospermia. A couple sought treatment for diminished ovarian reserve and male factor infertility using IVF. A mature oocyte was retrieved and was inseminated by intracytoplasmic sperm injection (ICSI), following recovery of spermatozoa by PESA. A good quality embryo was transferred. A viable pregnancy was confirmed by ultrasound scan. A healthy baby boy was delivered naturally at 37 weeks gestation. This study reports the first ongoing clinical pregnancy and subsequent birth resulting from ICSI of spermatozoa retrieved by PESA into an oocyte recovered during a natural cycle. The use of a combination of less invasive assisted reproductive techniques (PESA and nIVF) can overcome barriers to fertility.     

Electroejaculation and assisted reproductive technologies in the treatment of anejaculatory infertility

Objective: To determine the efficacy of electroejaculation in combination with assisted reproductive technology (ART).

Design: Case series.

Setting: University fertility program.

Patient(s): One hundred twenty-one consecutive couples seeking treatment of anejaculatory infertility.

Intervention(s): Electroejaculation with IUI, or gamete intrafallopian transfer or IVF.

Main Outcome Measure(s): Pregnancy and pregnancy outcome.

Result(s): Fifty-two couples became pregnant (43%), 39 by IUI alone (32.2%). Cycle fecundity for IUI was 8.7%. No difference in cycle fecundity was seen among ovarian stimulation protocols (clomiphene citrate, 7.6%, hMG, 13.2%, and natural cycle, 11.2%). Pregnancy was unlikely when the inseminated motile sperm count was <4 million. Female management protocol and etiology of anejaculation did not affect results. Patients undergoing IVF had higher cycle fecundity (37.2%) than did those undergoing IUI. The rates of spontaneous abortion and multiple gestations were 23% and 12%, respectively.

Conclusion(s): Electroejaculation with stepwise application of ART is effective in treating anejaculatory infertility. Intrauterine insemination with the least expensive monitoring protocol should be used for most couples, because use of more expensive monitoring did not improve results. It is cost-effective to bypass IUI and proceed directly to IVF in men who require anesthesia for electroejaculation and in those with a total inseminated motile sperm count < 4 million.