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19  Primary Ovarian Insuffciency

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In conclusion, POI involves the trio of amenorrhea, elevated gonadotropins, and estrogen defciency which are often associated with other long-term health consequences including vasomotor symptoms, vulvovaginal atrophy, psychological stress, increased risks of cardiovascular disease, decreased bone mineral density, and markedly reduced fertility. Our patient is one of the rare women with POI who was fortunate enough to have succeeded in the delivery of a healthy child through IVF. Like all women with POI, she must be followed up to ensure adequate treatment with hormonal replacement therapy aiming at supporting her gynecological, cardiovascular, bone, and sexual health.

References

1.\ Nelson LM. Clinical practice. Primary ovarian insuffciency. N Engl J Med. 2009;360:606–14. 2.\ Coulam CB, Adamson SC, Annegers LF. Incidence of premature ovarian failure. Obstet

Gynecol. 1986;67:604–6.

3.\ Hoek A, Schoemaker J, Drexhage HA. Premature ovarian failure and ovarian autoimmunity. Endocr Rev. 1997;18:107–34.

4.\ Nelson LM, Covington SN, Rebar RW. An update: spontaneous premature ovarian failure is not an early menopause. Fertil Steril. 2005;83:1327–32.

5.\ Bakalov VK, Vanderhoof VH, Bondy CA, Nelson LM. Adrenal antibodies detect asymptomatic autoimmune adrenal insuffciency in young women with spontaneous premature ovarian failure. Hum Reprod. 2002;17:2096–100.

6.\ Alzubaidi NH, Chapin HL, Vanderhoof VH, Calis KA, Nelson LM. Meeting the needs of young women with secondary amenorrhea and spontaneous premature ovarian failure. Obstet Gynecol. 2002;99:720–5.

7.\ Sullivan SD, Sarrel PM, Nelson LM. Hormone replacement therapy in young women with primary ovarian insuffciency and early menopause. Fertil Steril. 2016;106:1588–99.

Chapter 20

Tubal Factor

Kolbe Hancock and Pak H. Chung

Case

A 34-year-old nulligravid female presents with 13 months of infertility. She reports regular monthly menstrual periods and having coital exposure with the aid of urinary LH monitoring. Gynecologic history is signi cant for an abnormal Pap smear 5 years before presentation, which was followed by a benign colposcopic biopsy. Subsequent Pap smears have been normal. More importantly, she states that she was found to have a positive cervical chlamydial culture 8 years ago with a previous partner, which was treated successfully with oral antibiotics. Both she and her 36-year-old husband have had no signi cant medical problems.

Her initial work up in our Center revealed an anti-Mullerian hormone (AMH) level of 3.2 ng/mL, and an antral follicular count (AFC) of 12 on cycle day 3. Her husband’s semen analysis was normal. Hysterosalpingogram (HSG), however, revealed a normal uterine cavity and bilateral proximal tubal obstruction. Repeating the study with oral sedation was offered but the couple declined. Of note, she did not appear to be in much discomfort during the HSG. Mid-cycle transvaginal ultrasound demonstrated an 8 mm trilaminar endometrial lining without any evidence of ovarian cysts or an adnexal mass.

Management options were reviewed with the couple. A diagnostic laparoscopy could be considered to identify potential etiologies for proximal tubal obstruction. Her history of chlamydia and therefore possible tubal damage and/or pelvic/

K. Hancock

Reproductive Medicine and Ob/Gyn, Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Medical College of Cornell University, New York, NY, USA

P. H. Chung (*)

Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Medical College of Cornell University, New York, NY, USA

e-mail: pakchu@med.cornell.edu

© Springer Nature Switzerland AG 2023

127

P. H. Chung, Z. Rosenwaks (eds.), Problem-Focused Reproductive Endocrinology and Infertility, Contemporary Endocrinology, https://doi.org/10.1007/978-3-031-19443-6_20

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peritubal adhesions could be the cause for the obstruction and hence her infertility. The other option was to procced with in vitro fertilization (IVF) which would bypass the fallopian tubes. The patient declined surgery and decided to proceed with IVF. Ovarian stimulation with gonadotropins yielded 15 oocytes of which 12 fertilized. Endometrial thickness was 10 mm. A single high-grade blastocyst was transferred. The remaining six blastocysts underwent preimplantation genetic testing for aneuploidy (PGT-A) and were frozen.

She did not become pregnant with the fresh embryo transfer. Of the six PGT-A tested blastocysts, three were euploid. She was subsequently scheduled for a natural cycle frozen embryo transfer (FET). On the day of her LH surge, however, ultrasound examination revealed a thin layer of free fuid in the endometrial cavity, anding which persisted and was also visualized on the day of the scheduled transfer. Therefore FET was canceled.

Given all the ndings up to this point of her treatment, a laparoscopy was subsequently performed which con rmed moderate peritubal and pelvic adhesions, and bilateral hydrosalpinges. Lysis of adhesions and bilateral salpingectomies were performed uneventfully. Follow-up evaluation of the cavity demonstrated a normal endometrial stripe with no fuid. The patient subsequently underwent a natural cycle FET, promptly conceived and delivered a healthy baby at term.

Discussion

Tubal disease is identi ed in approximately 25–35% of female factor infertility [1]. Tubal factor may range from subtle damage within the lumen of the fallopian tube, to outright blockage associated with hydrosalpinges and/or peritubal adhesions. The gold standard for evaluating tubal factor is the HSG. A hydrosalpinx, caused by a fuid buildup within a blocked fallopian tube, leads to the characteristic sausage-like appearance, easily discerned on HSG and even on ultrasound. More than half of the hydrosalpinges are due to salpingitis from PID (chlamydia, gonorrhea, rarely tuberculosis), but they may also result from prior history of ectopic pregnancy, generalized peritonitis, and pelvic infammation of various etiologies (ruptured appendix is a notable example). However, one needs to recognize that tubal obstruction shown on HSG can sometimes be caused by tubal spasm of the interstitial region secondary to the irritation of the contrast on the tube [2]. Typically, if spasm is the etiology, patients may experience a higher degree of discomfort during the procedure. This may be relieved by sedatives allowinglling and spillage of dye through the fallopian tube.

Many variables need to be considered when counseling patients with tubal factor infertility. Chronological age of the female, ovarian reserve, presence of male factor, site and extent of the tubal disease, experience of the surgeon, and access to IVF are all factors to be discussed with the patient. Management of tubal factor infertility depends on the location of the pathology, i.e. proximal or distal, whether it is unilateral or bilateral, and the extent of the disease.

Presuming that all other factors are optimal, unilateral obstruction can be managed by expectant management, controlled ovarian hyperstimulation with or

20  Tubal Factor

129

without intrauterine insemination (IUI), surgery or IVF. Expectant management may involve ultrasound monitoring of ovulation in a natural cycle to determine if ovulation will occur on the side of the patent fallopian tube. If so, timed intercourse or intrauterine insemination (IUI) can be performed. Probability of conception when ovulation occurs on the blocked side is signi cantly lower. Superovulation using oral medications will improve the odds of having a mature follicle on the patent side. However, surgery or IVF are the only viable options in the setting of bilateral obstruction. Even with IVF where embryos are transferred to the uterine cavity, all patients with tubal factor should be counseled about a higher risk of having an ectopic pregnancy.

Proximal tubal obstruction, representing 10–25% of tubal diseases, can be treated with tubal cannulation under fuoroscopic guidance or by hysteroscopy with laparoscopic con rmation [3]. Tubal cannulation could relieve 85% of apparent obstructions although one-third of the initially reported cannulated tubes subsequently re-occluded. The treatment of choice for unilateral proximal obstruction has not been conclusively established. One study demonstrated that such patients had similar cumulative pregnancy rates after three cycles of controlled ovarian hyperstimulation and IUI when compared to patients with unexplained infertility [4].

Distal obstruction is usually associated with mbrial phimosis, hydrosalpinx, and/or pelvic adhesions. Laparoscopic neosalpingostomy is carried out by opening an obstructed tube. There is fair evidence that laparoscopic mbrioplasty or neosalpingostomy can be considered for treating distal obstruction (even with mild hydrosalpinx) in young women who have no other signi cant infertility factor. However, patients should be aware that pregnancy rates are directly correlated to the degree of tubal disease and are more favorable in patients with “good prognosis,” de ned in the literature as having limited lmy adhesions, mild tubal dilation <3 cm, thin pliable walls, and endosalpinx with preserved mucosal folds [5]. Speci cally, the intrauterine pregnancy rate after surgery for mild hydrosalpinges ranges from 58 to 77%, while the ectopic pregnancy rate after the procedure is reported to be between 2 and 8%. For comparison, in patients with more severe disease, the pregnancy success rate after surgery ranges from 0 to 22% with an ectopic rate ranging from 0 to 17%. Postoperatively, re-occlusion/reappearance of hydrosalpinx may occur, necessitating salpingectomy later.

In our practice, tubal surgery is only offered to patients with optimal ovarian reserve, absence of other compounding factors for infertility, mild tubal disease without signi cant pelvic adhesions, and who are reluctant to proceed with or have no access to IVF. Otherwise, IVF which overcomes tubal blockage is our preferred treatment.

In the setting of severe tubal damage with hydrosalpinges, there have been numerous studies demonstrating that these dilated tubes can have a detrimental effect on IVF success rates. There are multiple theories regarding the negative physiologic effects of hydrosalpinges on fertility. These include mechanical disruption or fushing of the embryo in the uterine cavity due to back fow of hydrosalpinx fuid which is infammatory in nature, increased endometrial peristalsis/contractions,

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decreased endometrial receptivity, altered endometrial blood fow, and the direct embryotoxic effect of the hydrosalpinx fuid on the embryo or sperm itself [6].

A meta-analysis on the impact of hydrosalpinx on IVF success demonstrated that hydrosalpinges caused a 50% decrease in pregnancy, implantation, and delivery rates, and a twofold increase in the spontaneous abortion rate [7]. Speci cally, it is thought that those with hydrosalpinges large enough to be visible on ultrasound might be more signi cantly affected. Several randomized controlled trials have shown that laparoscopic salpingectomy in women with hydrosalpinges achieved similar live birth rates as compared to women without hydrosalpinx [8]. Even in patients with unilateral hydrosalpinx, higher IVF pregnancy rates have been reported after unilateral salpingectomy. Therefore we generally recommend salpingectomy for patients with unilateral or bilateral hydrosalpinges before undergoing IVF.

Salpingectomy can be readily performed laparoscopically by sequentially coagulating and dividing the mesosalpinx, generally from the distal to proximal end of the fallopian tube. Upon reaching the proximal end, the tube is cauterized and divided as close to the cornua as possible. It should be noted that there had been reports suggesting that salpingectomy and tubal ligation are associated with subsequent diminished ovarian reserve; however the clinical signi cance of this observation has been debated. While it has been demonstrated that antral follicle count and blood fow to the ovary are reduced after laparoscopic salpingectomy performed for ectopic pregnancy [9], in one such study where IVF was performed before and after salpingectomy, no signi cant difference was found in the total dose or duration of gonadotropins administered, peak estradiol levels, number of oocytes retrieved or embryo quality between cycles or between the ovaries [10]. Regardless, during salpingectomy, great care should be exercised to resect as close to the tube as possible along the mesosalpinx in order to avoid compromising blood supply to the ovaries.

Proximal occlusion of the fallopian tube during laparoscopy can be an alternative to salpingectomy when severe pelvic adhesions preclude access to the entire tube for removal. Previously published randomized controlled trials demonstrated that proximal tubal occlusion was effective in restoring IVF pregnancy rates in women with hydrosalpinges [11]. In addition, it has not been shown that this technique had any negative impact on ovarian reserve [12]. The preferred method for occlusion, cautery or mechanical clips, is debated. A randomized controlled trial found that bipolar cautery had an adverse effect on ovarian volume and antral follicle counts while mechanical clips did not [13]. However, neither technique was associated with appreciable changes in day-3 FSH, estradiol, inhibin-B, or anti-Mullerian hormone levels. Another theoretical concern of proximally occluding the tube is that it may lead to increased swelling of the hydrosalpinx, as the fuid is precluded from draining into the uterus, which in turn may lead to increased incidence of pelvic pain and risk of torsion.

Ultrasound-guided aspiration of hydrosalpinges at the time of oocyte retrieval is a less invasive option. The literature supporting such an approach is sparse, with conficting results in two small retrospective studies [14, 15]. A randomized controlled study comparing ultrasound-guided aspiration to a nontreated control group reported signi cantly higher clinical pregnancy rates of 31.3% with aspiration