Planned oocyte cryopreservation for fertility preservation

Oocyte cryopreservation opens up opportunities for women to preserve fertility when it is necessary to postpone pregnancy. After the advent of vitrification, the results of oocyte cryopreservation were significantly improved compared to conventional slow-freezing. Through these improvements, oocyte cryopreservation was introduced to overcome a decline in fecundity due to an increase in age, and this modality is defined as planned oocyte cryopreservation.Current Concepts: Oocytes cryopreserved through vitrification appear to result in similar clinical pregnancy rates and live birth rates compared to fresh oocytes, though the evidence is still limited. It has been reported that the live birth rate increases when the planned oocyte cryopreservation is performed at a younger age. Obstetrical and neonatal outcomes appear similar between vitrified and fresh oocytes.Discussion and Conclusion: Preliminary data supports planned oocyte cryopreservation as a feasible modality resulting in fertility preservation and subsequent live births. The fact that performing the procedure at a younger age can increase the oocyte yield, oocyte efficacy, and live birth rate can be discussed along with patient consultation. However, as there is still a lack of data on the standardized live birth rate, the number of oocytes to be collected, and the long-term effect on the children; more well-designed studies are needed to improve counseling and decision-making in patients seeking this treatment.

Effects and safety of COVID-19 vaccination on assisted reproductive technology and pregnancy: A comprehensive review and joint statements of the KSRM, the KSRI, and the KOSAR / 대한생식의학회지

Humanity is in the midst of the coronavirus disease 2019 (COVID-19) pandemic, and vaccines—including mRNA vaccines—have been developed at an unprecedented speed. It is necessary to develop guidelines for vaccination for people undergoing treatment with assisted reproductive technology (ART) and for pregnancy-related situations based on the extant laboratory and clinical data. COVID-19 vaccines do not appear to adversely affect gametes, embryos, or implantation; therefore, active vaccination is recommended for women or men who are preparing for ART. The use of intravenous immunoglobulin G (IVIG) for the treatment of immune-related infertility is unlikely to impact the effectiveness of the vaccines, so COVID-19 vaccines can be administered around ART cycles in which IVIG is scheduled. Pregnant women have been proven to be at risk of severe maternal and neonatal complications from COVID-19. It does not appear that COVID-19 vaccines harm pregnant women or fetuses; instead, they have been observed to deliver antibodies against severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) to the fetus. Accordingly, it is recommended that pregnant women receive COVID-19 vaccination. There is no rationale for adverse effects, or clinical cases of adverse reactions, in mothers or neonates after COVID-19 vaccination in lactating women. Instead, antibodies to SARS-CoV-2 can be delivered through breast milk. Therefore, breastfeeding mothers should consider vaccination. In summary, active administration of COVID-19 vaccines will help ensure the safe implementation of ART, pregnancy, and breastfeeding.

The impact of COVID-19 on human reproduction and directions for fertility treatment during the pandemic / 대한생식의학회지

Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly, resulting in a pandemic. The virus enters host cells through angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2). These enzymes are widely expressed in reproductive organs; hence, coronavirus disease 2019 (COVID-19) could also impact human reproduction. Current evidence suggests that sperm cells may provide an inadequate environment for the virus to penetrate and spread. Oocytes within antral follicles are surrounded by cumulus cells, which rarely express ACE2 and TMPRSS2. Thus, the possibility of transmission of the virus through sexual intercourse and assisted reproductive techniques seems unlikely. Early human embryos express coronavirus entry receptors and proteases, implying that human embryos are potentially vulnerable to SARS-CoV-2 in the early stages of development. Data on the expression of ACE2 and TMPRSS2 in the human endometrium are sparse. Moreover, it remains unclear whether SARS-CoV-2 directly affects the embryo and its implantation. A study of the effect of SARS-CoV-2 on pregnancy showed an increase in preterm delivery. Thus, vertical transmission of the virus from mother to fetus in the third trimester is possible, and further data on human reproduction are required to establish this possibility. Based on analyses of existing data, major organizations in this field have published guidelines on the treatment of infertility. Regarding these guidelines, despite the COVID-19 pandemic, reproductive treatment is crucial for the well-being of society and must be continued under suitable regulations and good standard laboratory practice protocols.

A comprehensive review and the pharmacologic management of primary dysmenorrhea

Dysmenorrhea is the most common gynecologic condition in women during the reproductive period. Severe dysmenorrhea pain affects their social activities, sleep, and quality of life. Nevertheless, the proportion of women with dysmenorrhea do not receive adequate medical counseling or pharmacological treatments. Primary dysmenorrhea is diagnosed clinically, and the secondary causes that can cause pelvic pain should be identified. The treatment of choice for primary dysmenorrhea is non-steroidal anti-inflammatory drugs (NSAIDs). In order to maximize the therapeutic effect, it is necessary to ensure that the appropriate medication is administered in a proper way. NSAIDs can cause adverse effects, including gastrointestinal disorders. If side effects occur or are anticipated with NSAIDs, the use of hormonal contraceptives may be recommended when contraception is considered. In addition to these pharmacological treatments, heat, dietary, and behavioral therapies have been tried and reported to have some effects. However, further research is required for robust conclusions.

A comprehensive review and the pharmacologic management of primary dysmenorrhea

Dysmenorrhea is the most common gynecologic condition in women during the reproductive period. Severe dysmenorrhea pain affects their social activities, sleep, and quality of life. Nevertheless, the proportion of women with dysmenorrhea do not receive adequate medical counseling or pharmacological treatments. Primary dysmenorrhea is diagnosed clinically, and the secondary causes that can cause pelvic pain should be identified. The treatment of choice for primary dysmenorrhea is non-steroidal anti-inflammatory drugs (NSAIDs). In order to maximize the therapeutic effect, it is necessary to ensure that the appropriate medication is administered in a proper way. NSAIDs can cause adverse effects, including gastrointestinal disorders. If side effects occur or are anticipated with NSAIDs, the use of hormonal contraceptives may be recommended when contraception is considered. In addition to these pharmacological treatments, heat, dietary, and behavioral therapies have been tried and reported to have some effects. However, further research is required for robust conclusions.

A comprehensive review and the pharmacologic management of primary dysmenorrhea

Dysmenorrhea is the most common gynecologic condition in women during the reproductive period. Severe dysmenorrhea pain affects their social activities, sleep, and quality of life. Nevertheless, the proportion of women with dysmenorrhea do not receive adequate medical counseling or pharmacological treatments. Primary dysmenorrhea is diagnosed clinically, and the secondary causes that can cause pelvic pain should be identified. The treatment of choice for primary dysmenorrhea is non-steroidal anti-inflammatory drugs (NSAIDs). In order to maximize the therapeutic effect, it is necessary to ensure that the appropriate medication is administered in a proper way. NSAIDs can cause adverse effects, including gastrointestinal disorders. If side effects occur or are anticipated with NSAIDs, the use of hormonal contraceptives may be recommended when contraception is considered. In addition to these pharmacological treatments, heat, dietary, and behavioral therapies have been tried and reported to have some effects. However, further research is required for robust conclusions.

Cumulative live birth rate after up to three consecutive embryo transfer cycles in women with poor ovarian response / 대한생식의학회지

Objective@#In the present study, we aimed to retrospectively evaluate the cumulative live birth rate (LBR) after up to three consecutive embryo transfer (ET) cycles, either fresh or frozen, in women with expected poor ovarian response (ePOR). @*Methods@#We selected 115 women who entered the first in vitro fertilization (IVF) cycle between August 2013 and July 2016. The women were divided into an ePOR group (37 women) and a non-ePOR group (78 women). All women in the ePOR group were ≥40 years old or had serum anti-Müllerian hormone levels of less than 1.1 ng/mL at the time of the first IVF cycle. Live birth outcomes were monitored until December 2017. The cumulative LBR (with both conservative and optimistic estimates) was calculated according to the serial number of ET cycles. @*Results@#After up to three ET cycles, the overall cumulative LBR was significantly lower in the ePOR group than in the non-ePOR group (conservative estimate, 10.8% vs. 44.9%, respectively; optimistic estimate, 14.7% vs. 56.1%, respectively; log-rank test, p=0.003). @*Conclusion@#Women with ePOR exhibited a lower cumulative LBR than women in the non-ePOR group, and this information should be provided to ePOR women during counseling before starting IVF.

Management of endometriosis-related infertility: Considerations and treatment options / 대한생식의학회지

Endometriosis is a common inflammatory disease in women of reproductive age and is one of the major causes of infertility. Endometriosis causes a sustained reduction of ovarian reserve through both physical mechanisms and inflammatory reactions, which result in the production of reactive oxygen species and tissue fibrosis. The severity of endometriosis is related to ovarian reserve. With regard to infertility treatment, medical therapy as a neoadjuvant or adjuvant to surgical therapy has no definite beneficial effect. Surgical treatment of endometriosis can lead to ovarian injury during the resection of endometriotic tissue, which leads to the deterioration of ovarian reserve. To overcome this disadvantage, a multistep technique has been proposed to minimize the reduction of ovarian reserve. When considering surgical treatment of endometriosis in patients experiencing infertility, it should be kept in mind that ovarian reserve can be reduced both due to endometriosis itself and by the process of removing endometriosis. In cases of mild- to moderate-stage endometriosis, intrauterine insemination with ovarian stimulation after surgical treatment may increase the likelihood of pregnancy. In cases of severe endometriosis, the characteristics of the patient should be considered in a multidisciplinary manner to determine the prioritization of treatment modalities, including surgical treatment and assisted reproduction methods such as in vitro fertilization. The risk of cancer, complications after pregnancy, and infection during oocyte retrieval should also be considered when making treatment decisions.

Evaluation of normal morphology, DNA fragmentation, and hyaluronic acid binding ability of human spermatozoa after using four different commercial media for density gradient centrifugation / 대한생식의학회지

OBJECTIVE: Density gradient centrifugation (DGC) is frequently used to isolate high-motility fractions of spermatozoa. We compared the efficacy of four DGC media in terms of the percentage of morphologically normal spermatozoa, DNA fragmentation level, and hyaluronic acid (HA) binding ability. METHODS: Thirty men with a total motile spermatozoa count >80 million participated. Semen samples were divided into four aliquots, which were processed using PureSperm, PureCeption, Sidney, and SpermGrad media, respectively. The DNA fragmentation level was measured using the Halosperm assay kit and HA binding ability was measured using the HBA assay kit. RESULTS: The mean percentage of morphologically normal spermatozoa was significantly enhanced after DGC using all four media (10.3%, 9.9%, 9.8%, and 10.7%, respectively; p0.05). HA binding ability did not change after DGC using any of the four media. CONCLUSION: The four media were equally effective for obtaining a sperm fraction with highly motile, morphologically normal sperm. PureSperm, PureCeption, and SpermGrad media were equally effective for acquiring a sperm fraction with less DNA fragmentation.

A retrospective analysis of the follicle-stimulating hormone starting dose in expected normal responders undergoing their first in vitro fertilization cycle: proposed dose versus empiric dose / 대한생식의학회지

OBJECTIVE: The purpose of this retrospective study was to evaluate the appropriateness of various follicle-stimulating hormone (FSH) starting doses in expected normal responders based on the nomogram developed by La Marca et al. METHODS: A total of 117 first in vitro fertilization cycles performed from 2011 to 2017 were selected. All women were expected normal responders and used a recombinant FSH and flexible gonadotropin-releasing hormone antagonist protocol. The FSH starting dose was empirically determined (150, 225, or 300 IU). The FSH starting dose indicated by La Marca's nomogram was determined using female age and serum anti-Müllerian hormone or basal FSH levels. If the administered dose was exactly the same as the proposed dose, the cycle was assigned to the concordant group (34 cycles). If not, it was assigned to the discordant group (83 cycles). Optimal ovarian response was defined as a total of 8–14 oocytes, hypo-response as 14 oocytes. RESULTS: Between the concordant and discordant group, ovarian response (optimal, 32.4% vs. 27.7%; hypo-response, 55.9% vs. 54.2%; and hyper-response, 11.8% vs. 18.1%) and the number of total or mature oocytes were similar. Ovarian hyperstimulation syndrome was rare in both groups (0% vs. 1.2%). The implantation rate, clinical pregnancy rate, miscarriage rate, and live birth rate were all similar. CONCLUSION: The use of the proposed FSH starting dose determined using La Marca's nomogram did not enhance the optimal ovarian response rate or pregnancy rate in expected normal responders. Individualization of the FSH starting dose by La Marca's nomogram appears to have no distinct advantages over empiric choice of the dose in expected normal responders.

The serum estradiol/oocyte ratio in patients with breast cancer undergoing ovarian stimulation with letrozole and gonadotropins

OBJECTIVE: To investigate the patterns of estradiol-oocyte ratio (EOR) and estradiol-mature oocyte ratio (EMOR) in patients with breast cancer undergoing controlled ovarian stimulation (COS) using letrozole and gonadotropins for fertility preservation. METHODS: This retrospective study included 32 breast cancer patients underwent COS for fertility preservation and no patients had previously undergone gonadotoxic treatments. Basal characteristics and in vitro fertilization (IVF) outcomes were compared according to the age of women (age < 35 vs. age ≥35) and the starting phase of ovarian stimulation (early follicular phase vs. late follicular phase vs. luteal phase). RESULTS: Patients who were administered with a letrozole-combined regimen, the peak serum estradiol (E2) was maintained at a low level (386.3±346.9 pg/mL). EOR was 52.4±78.8 pg/mL, and EMOR was 71.0±41.2 pg/mL. When the 2 groups were compared according to the age of women (age < 35 vs. age ≥35), EOR was 34.5 (22.2–46.5) pg/mL and 40.7 (19.3–65.3) pg/mL, respectively; EMOR was 79.8 (40.8–90.6) pg/mL and 68.8 (44.5–85.9) pg/mL, respectively. There was no significant difference in the IVF outcomes. When the 2 groups were compared according to the starting phase of ovarian stimulation, there were no significant differences in IVF outcomes, EOR and EMOR among the groups. CONCLUSION: Measuring the peak E2 concentration in breast cancer patients undergoing IVF for fertility preservation with a co-treatment of letrozole allows for the prediction of the numbers of oocytes and mature oocytes.

Successful in Vitro Fertilization and Embryo Transfer after Transplantation of Cryopreserved Ovarian Tissue: Report of the First Korean Case

For patients at risk of premature ovarian failure with cancer treatment, it is an important option to re-implant the ovarian tissue (OT) after cryopreservation to preserve endocrine function and fertility. With this technique, about 30% of pregnancy success rate and about 90 live births have been reported to date. However, there has been no case report of successful in vitro fertilization (IVF) and embryo transfer (ET) with oocytes collected from transplanted cryopreserved OT in Korea. We report a 30-year old woman with rectal cancer who underwent IVF and ET after cryopreserved OT thawing and re-implantation. She has been diagnosed with stage IIIC rectal cancer after surgery, and right ovary was removed and cryopreserved between cycles of chemotherapy. After completion of chemotherapy and radiotherapy, the patient underwent orthotopic transplantation of cryopreserved OTs. Three months after transplantation, the serum follicle-stimulating hormone level decreased from 91.11 mIU/mL to 43.69 mIU/mL. Thereafter, the patient underwent 11 ovarian stimulation cycles, and in 7 cycles, follicle growth was observed at the OT graft site. In one of these cycles, the oocyte was successfully retrieved and one embryo was transplanted after IVF. The patient was not pregnant, but the cryopreservation of OT can save the fertility after anticancer chemotherapy.

Gonadotropin releasing hormone antagonist administration for treatment of early type severe ovarian hyperstimulation syndrome: a case series

OBJECTIVE: To report an efficacy of gonadotropin releasing hormone (GnRH) antagonist administration after freezing of all embryos for treatment of early type ovarian hyperstimulation syndrome (OHSS). METHODS: In 10 women who developed fulminant early type OHSS after freezing of all embryos, GnRH antagonist (cetrorelix 0.25 mg per day) was started at the time of hospitalization and continued for 2 to 4 days. Fluid therapy and drainage of ascites was performed as usual. RESULTS: Early type OHSS was successfully treated without any complication. At hospitalization, the median (95% confidence interval [CI]) of the right and the left ovarian diameter was 10.0 cm (7.6 to 12.9 cm) and 8.5 cm (7.5 to 12.6 cm). After completion of GnRH antagonist administration, it was decreased to 7.4 cm (6.2 to 10.7 cm) (P=0.028) and 7.8 cm (5.7 to 12.2 cm) (P=0.116), respectively. The median duration of hospital stay was 6 days (3 to 11 days). Trans-abdominal drainage of ascites was performed in 2 women and drainage of ascites by percutaneous indwelling catheter was performed in 4 women. No side effect of GnRH antagonist was noted. CONCLUSION: GnRH antagonist administration appears to be safe and effective for women with fulminant early type OHSS after freezing all embryos. Optimal dose or duration of GnRH antagonist should be further determined.

The efficacy of intrauterine instillation of granulocyte colony-stimulating factor in infertile women with a thin endometrium: A pilot study / 대한생식의학회지

OBJECTIVE: The study aimed to investigate the efficacy of intrauterine instillation of granulocyte colony-stimulating factor (G-CSF) on the day of ovulation triggering or oocyte retrieval in infertile women with a thin endometrium. METHODS: Fifty women whose endometrial thickness (EMT) was ≤8 mm at the time of triggering during at least one previous in vitro fertilization (IVF) cycle and an index IVF cycle were selected. On the day of triggering (n=12) or oocyte retrieval (n=38), 300 µg of G-CSF was instilled into the uterine cavity. RESULTS: In the 50 index IVF cycles, the mean EMT was 7.2±0.6 mm on the triggering day and increased to 8.5±1.5 mm on the embryo transfer day (p<0.001). The overall clinical pregnancy rate was 22.0%, the implantation rate was 15.9%, and the ongoing pregnancy rate was 20%. The clinical pregnancy rate (41.7% vs. 15.8%), the implantation rate (26.7% vs. 11.7%), and the ongoing pregnancy rate (41.7% vs. 13.2%) were higher when G-CSF was instilled on the triggering day than when it was instilled on the retrieval day, although this tendency was likewise not statistically significant. Aspects of the stimulation process and mean changes in EMT were similar in women who became pregnant and women who did not. CONCLUSION: Intrauterine instillation of G-CSF enhanced endometrial development and resulted in an acceptable pregnancy rate. Instillation of G-CSF on the triggering day showed better outcomes. G-CSF instillation should be considered as a strategy for inducing endometrial growth and good pregnancy results in infertile women with a thin endometrium.