In Contemporary Reproductive Medicine Human Beings are Not Yet Dispensable.

In the past few years almost every aspect of an IVF cycle has been investigated, including research on sperm, color doppler in follicular studies, prediction of embryo cleavage, prediction of blastocyst formation, scoring blastocyst quality, prediction of euploid blastocysts and live birth from blastocysts, improving the embryo selection process, and for developing deep machine learning (ML) algorithms for optimal IVF stimulation protocols. Also, artificial intelligence (AI)-based methods have been implemented for some clinical aspects of IVF, such as assessing patient reproductive potential and individualizing gonadotropin stimulation protocols. As AI has the inherent capacity to analyze "Big" data, the goal will be to apply AI tools to the analysis of all embryological, clinical, and genetic data to provide patient-tailored individualized treatments. Human skillsets including hand eye coordination to perform an embryo transfer is probably the only step of IVF that is outside the realm of AI & ML today. Embryo transfer success is presently human skill dependent and deep machine learning may one day intrude into this sacred space with the advent of programed humanoid robots. Embryo transfer is arguably the rate limiting step in the sequential events that complete an IVF cycle. Many variables play a role in the success of embryo transfer, including catheter type, atraumatic technique, and the use of sonography guidance before and during the procedure of embryo transfer. In contemporary Reproductive Medicine human beings are not yet dispensable.

Intrauterine Insemination: Fundamentals Revisited.

Intrauterine insemination (IUI) is an assisted conception technique that involves the deposition of a processed semen sample in the upper uterine cavity, overcoming natural barriers to sperm ascent in the female reproductive tract. It is a cost-effective, noninvasive first-line therapy for selected patients with functionally normal tubes, and infertility due to a cervical factor, anovulation, moderate male factor, unexplained factors, immunological factor, and ejaculatory disorders with clinical pregnancy rates per cycle ranging from 10 to 20%. It, however, has limited use in patients with endometriosis, severe male factor infertility, tubal factor infertility, and advanced maternal age ≥ 35 years. IUI may be performed with or without ovarian stimulation. Controlled ovarian stimulation, particularly with low-dose gonadotropins, with IUI offers significant benefit in terms of pregnancy outcomes compared with natural cycle or timed intercourse, while reducing associated COH complications such as multiple pregnancies and ovarian hyperstimulation syndrome. Important prognostic indicators of success with IUI include age of patient, duration of infertility, stimulation protocol, infertility etiology, number of cycles, timing of insemination, number of preovulatory follicles on the day of hCG, processed total motile sperm > 10 million, and insemination count > 1 × 106 with > 4% normal spermatozoa. Alternative insemination techniques, such as Fallopian tube sperm perfusion, intracervical insemination, and intratubal insemination, provide no additional benefit compared to IUI. A complete couple workup that includes patient history, physical examination, and clinical and laboratory investigations is mandatory to justify the choice in favor of IUI and guide alternative patient management, while individualizing the treatment protocol according to the patient characteristics with a strict cancelation policy to limit multi-follicular development may help optimize IUI pregnancy outcomes.

Is Laparoscopic Power Morcellation of Fibroids a Cardinal Sin in 2017?

The diagnosis of an unsuspected leiomyosarcoma after hysterectomy for the treatment of a presumed benign leiomyoma is a rare but highly clinically significant event. In order to facilitate removal of large uterine specimens using a minimally invasive surgical approach, morcellation with extraction in pieces is often performed. In the event of unsuspected malignancy, this may result in abdominal dispersion of the tumor and contribute to poorer survival. Modern surgical innovations always work toward improving minimally invasive strategies. Laparoscopy, rooted in practices for years, supplanted laparotomy for many indications. For extraction of large uteri, morcellation is currently the only way to externalize surgical specimens (myomas, uteri), without increasing the skin opening while allowing to reduce postoperative complications when compared to laparotomy. However, in 2014, the Food and Drug Administration warned against the use of uterine morcellation because of an oncological risk. Some practicing academicians have challenged this recommendation. The incidence of uterine sarcomas is still poorly identified and preoperative diagnostic facilities remain inadequate. The small number of retrospective studies currently available do not reinforce any recommendation. The evaluation of morcellation devices and the improvement of preoperative diagnostic modalities (Imaging, preoperative Biopsy) are being improvised continually so as to minimize the oncological risks. Even during conventional myomectomy, tissue spillage occurs during resection of leiomyoma(s). Adverse oncologic outcomes of tissue morcellation should be mitigated through improved patient selection, preoperative investigations, and novel techniques that minimize tissue dispersion. Preoperative endometrial biopsy and cervical assessment to avoid morcellation of potentially detectable malignant and premalignant conditions is recommended.

Viral Hepatitis and Assisted Reproduction.

Infertility treatment in couples where one or both parents are infected with hepatitis raises many concerns about transmission of the infection to the baby, laboratory technicians, and medical staff, and contamination of other gametes/embryos that are from virus-free parents in the same laboratory. Exposure to the other partner is only a risk when the couple's hepatitis status is discordant. The management of infertility, in association with HBV or HCV, has sparked debates about the potential risk of spread of infection to virus-free individuals, embryos, and/or semen. This risk can only be minimized or eliminated by the use of SOPs for safety in fertility clinics and by the use of proper initial detection and segregation of potentially hazardous materials. HBV may interfere with the development of embryos and even result in abortion and other adverse outcomes. Although sexual transmission of HCV is very low, in subfertile or infertile couples sperm washing should be used to treat HCV-positive semen before ART. Testing for HBsAg and HCV should be offered to high-risk infertile couples seeking fertility therapy to reduce the potential risk of transmission to an uninfected partner, baby, staff members, and disease-free gametes and embryos in the same laboratory. Testing for HIV, HBsAg, and HCV status should be performed on the couple prior to cryopreservation of semen or embryos.

Getting Older Women Pregnant: Contemporary Thoughts.

For women of advanced age with abnormally increased FSH levels, standardized hormonal stimulation often represents a cost-intensive procedure with a low success rate. It is well established now that with mild ovarian stimulation, there is a greater percentage of good-quality eggs (although a smaller number) than with higher-dose conventional stimulation. Mild stimulation protocols reduce the mean number of days of stimulation, the total amount of gonadotropins used and the mean number of oocytes retrieved. The proportion of high-quality and euploid embryos seems to be higher compared with conventional stimulation protocols, and the pregnancy rate per embryo transfer is comparable. Moreover, the reduced costs, the better tolerability for patients and the less time needed to complete an IVF cycle make mild approaches clinically and cost-effective over a given period of time. The low number of embryos available for transfer poses a great challenge in the management of older women going in for IVF. A potential management of these older women is to create a sufficient pool of embryos by accumulating vitrified good-grade embryos over several minimal stimulation and natural cycles. At the end of the accumulation process, these embryos can be subjected to a preimplantation genetic screening using next-generation sequencing and then the pool would have only chromosomal normal embryos with maximal chances of implantation. This would potentially make the chances of success for older women similar to normal responders. This management, however, is unthinkable without an outstanding vitrification program. The option of accumulating embryos has become a promising reality with the advent of vitrification technologies.

Social Egg Freezing: Developing Countries Are Not Exempt.

Non-medical egg freezing has only been available for about the last 5 years, as new vitrification techniques have made the success rates for actual conception more reliable than the earlier method of slow freezing. The improved outcomes of new technologies of vitrification and intra-cytoplasmic sperm injection (ICSI) have led to the marketing of egg freezing for non-medical reasons, whereby women are offered the possibility of preserving their eggs until such time as they wish to have a child. For many women today, it is not cancer but the simple passage of time that robs them of their chance of motherhood. Social, educational, emotional and financial pressures often lead them to delay trying to start a family until their late thirties, by which time the chance of success is very low. Women at age 40 face a 40 % chance of miscarriage if they can get pregnant at all, and by the age of 45, the risk of miscarriage is 75 %. Donor eggs are not an option for many because of supply constraints and ethical and cultural concerns. Freezing a woman's eggs at age 30 literally "freezes in time" her fertility potential and gives her the chance of a healthy pregnancy at a time of her choosing. Despite the initial reactions of disapproval, more and more fertility clinics are now offering oocyte cryopreservation to healthy women in order to extend their reproductive options. This procedure is now becoming popular even in developing economies, and egg freezing in major Indian Metros is now routine.

Yes, It is Possible.

Human immunodeficiency virus-serodiscordant couples are actively seeking reproductive assistance and often consider or practice unsafe measures to achieve pregnancy. Reproductive issues and concerns unique to these couples need to be addressed before treatment. Assisted reproduction techniques can minimize the risk of infection and complete families associated with serodiscordant couples. Since 1987, more than 4000 published attempts have been reported in which processed spermatozoa from HIV-seropositive men were used to establish pregnancy in HIV-seronegative women. When the female partner is HIV positive, intrauterine insemination (IUI) will suffice in order to prevent horizontal infection. However, when the male partner is HIV positive, a technique developed in Milan over 15 years ago, involving sperm washing, is used in order to minimize infection of the healthy partner. Some couples need further treatment, due to inherent infertility, with advanced reproductive technology (ART) procedures, such as IVF or ICSI. Recent innovative approaches such as pre-exposure prophylaxis (PrEP) with antiretroviral drugs may reduce further the susceptibility of the uninfected female partner. Numerous ART centers worldwide treat these couples. Most centers are equipped with separate laboratory space for collecting specimens from infected patients and provide separate storage tanks for freezing infected gametes and embryos in order to protect other patients using the facility. There are no reports of HIV infection of laboratory personnel resulting from processing the gametes/embryos for serodiscordant couples using current laboratory protocols. Cross-contamination of the gametes or embryos of other couples in the same laboratory has also not been reported. The risk is theoretical only, particularly when standard universal precautions are used.

Primum Non Nocere.

Surgical ovarian wedge resection was the first established treatment for women with anovulatory polycystic ovary syndrome (PCOS) but was largely abandoned both due to the risk of postsurgical adhesions and the introduction of medical ovulation induction. Laparoscopic ovarian drilling (LOD) is an alternative method to induce ovulation in PCOS patients with clomiphene citrate resistance instead of gonadotropins. Surgical therapy with LOD may avoid or reduce the need for gonadotropins or may facilitate their use. However, the procedure, though effective, can be traumatic on the ovaries, which may cause postoperative adhesions and/or diminished ovarian reserve. In over-enthusiastic hands, this day-care procedure might lead to iatrogenic premature ovarian failure in young women. Some trials have compared LOD with gonadotropins, but, because of variations in study design and small sample size, the results are inconsistent and definitive conclusions about the relative efficacy of LOD and gonadotropins cannot be extracted from the individual studies. Today, evidence-based reviews conclude that there is no evidence of a significant difference in rates of clinical pregnancy, live birth or miscarriage in women with clomiphene-resistant PCOS undergoing LOD compared to other medical treatments. The reduction in multiple pregnancy rates in women undergoing LOD is the only pro-LOD argument. However, there are ongoing serious concerns about the long-term effects of LOD on ovarian function.

Oral Drugs for Unexplained Infertility.

Of the infertile couples unable to conceive without any identifiable cause, 30 % are defined as having unexplained infertility. Management depends on duration of infertility and age of female partner. The treatment of unexplained infertility is empirical, and many different regimens have been used. Among these are expectant management, ovarian stimulation with clomiphene citrate, gonadotropins and aromatase inhibitors, fallopian tube sperm perfusion, tubal flushing, intrauterine insemination, gamete intrafallopian transfer, and IVF. The first approach to treatment of unexplained infertility generally is the use of drugs that stimulate oocyte production. For over four decades, the first-line treatment for ovarian stimulation in unexplained infertility has been clomiphene citrate. Multiple reports suggest that aromatase inhibitors may be effective alternative agents for ovarian stimulation in couples with unexplained infertility. Their administration is reported to be associated with monofollicular development in most cases, which may result in enhanced fertility and a reduced risk of ovarian hyperstimulation and multiple births, as compared to current standard therapies such as gonadotropin and clomiphene. Despite world evidence to the contrary, letrozole has been banned for use for infertility management in India since 2011.

Erratum to: Should We be More "Open" About Publishing Research?

[This corrects the article DOI: 10.1007/s13224-014-0624-2.].